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Movement disorders as a manifestation of nonketotic hyperglycemia
The Journal of Emergency Medicine, Vol. 7. pp. 359-364,
Printed In the USA
1989
MOVEMENT DISORDERS AS A MANIFESTATION OF NONKETOTIC HYPERGLYCEMIA Clark A. Morres,
MD,
Cpt., MC, USA, and Daniel J. Dire, MD,Cpt., MC, USA
Department of Emergency
Medicine, Emergency Medicine Residency Program, Darnall Army Community Hospital, Ft. Hood, Texas 76544-5063 Reprint address: Daniel J. Dire, MD, Cpt., MC, Department of Emergency Medicine, Darnall Army Hospital, Ft. Hood, TX 76544-5063
0 Abstract - Movement disorders are well-known presenting signs of metabolic disorders. Focal motor abnormalities may be the chief initial presentation of diabetes mellitus in the nonketotic hyperglycemic state in 6% of patients. Nonketotic hyperglycemia (NKH), in particular, may manifest any of a wide variety of movement disorders. These have been described as focal seizures, epllepsia partialis continua, myoclonus, and opsoclonia. There are descriptions of movement disorders in hyperglycemia that are similar to the coarse flapping tremor of asterlxls, the posturing of paroxysmal kinetogenic choreoathetosis, and of “fencing (stance) seizures.” Disorders of facial motor function including aphasia, facial muscle twitching and jerking, and disorders of muscular tone have been described. These may include hemiparesis and hemiplegias as well as increased tone, in some cases mimicking the nuchal rigidity of meningitis. The movement disorders in NKH may mimic cerebral vascular accidents, meningitis, or psychiatric disorders, as well as various types of seizures. Clinicians may be able to avoid expensive and time-consuming diagnostic evaluations to rule out NKH in patients with movement disorders. We present two patients with focal motor abnormalities associated with nonketonic hyperglycemia and review the pertinent literature.
of movement disorders are known manifestations of metabolic disorders including hepatic encephalopathy, hyponatremia, hypocalcemia, uremia, and hypoxia (l-3). Hyperglycemia is the most common metabolic disturbance that can result in focal motor seizures and other focal motor phenomena (2,4). Numerous reports in the neurological literature and more rare reports in the general medical literature draw attention to the importance of this entity (2). These reports also depict a wide variation in the kinds of motor disturbances observed. Although disorders of movement alone can be the presenting sign of diabetes mellitus, no reports or reviews of this clinical manifestation of nonketotic hyperglycemia (NKH) appear in the emergency medicine literature. The importance of recognizing these movement disorders is crucial since mortality is as high as 40% to 60% when hyperglycemia progresses to hyperosmolar coma (596).
• I Keywords-movement disorders; focal seizures; nonketotic hyperglycemia; seizures; hyperglycemia
A 26-year-old black male who was in excellent health with no history of diabetes or seizures was evaluated in the emergency department (ED) three separate times over a 30-hour period for a complaint of shaking in his right arm and right leg. At his first presentation, the patient stated that the shaking had begun spontaneously while he was in his sleeping bag outdoors on the ground during a cold night. The shaking subsided spontaneously after several minutes but recurred the next morning, prompting him to seek medical treatment in the ED. The shaking had subsided prior to evaluation and thus was not witnessed. The patient’s physical examination was normal. He
INTRODUCTION
Neurologic abnormalities
that include a wide range
The opinions or assertions contained herein are those of the authors and should not be construed as official or representing the opinions of the Department of the Army or the Department of Defense.
CASE 1
RECEIVED:12 April 1988; FINALSUBMISSION RECEIVED:6 December ACCEPTED: 13 December 1988
1988;
0736-4679/89 $3.00 + .OO
360
was discharged with a diagnosis of “nonspecific muscle contractions,” possibly related to the cold ambient temperatures. The patient returned to the ED 22 hours later with the same complaints. While being evaluated, he was asked to move his right leg. This precipitated a shaking episode resembling myoclonic muscle contractions that was thought by the examining physician to be under voluntary control. The remainder of the physical examination was normal. There was no positive Babinski sign, and deep tendon reflexes were normal even during the shaking episode. The patient had several similar episodes while in the ED, lasting from 20 seconds to 2 minutes. The patient’s shaking stopped immediately when he was ordered to stand at attention by a superior officer. Several psychosocial stresses were identified after interviewing co-workers and supervisors to include a pending disciplinary action for drug abuse, personality disputes, and lack of military bearing. The patient was discharged with the diagnosis of “possible pseudoseizure” perhaps related to an antisocial personality disorder. Follow-up consultations with the community mental health department and social work department were arranged. The patient presented to the ED for a third time, again with shaking and jerking movements of the right leg and right arm lasting 5 to 10 minutes at a time. He had now developed polyuria and polydipsia. He had been incontinent of urine just prior to arrival. The physical examination revealed an alert, oriented black male. Vital signs were blood pressure, 142/90 mm Hg; pulse, 88 per minute; and temperature, 35.2”C (95.3”F). The patient was noted to have a shaking in the right arm and leg. These movements subsided without treatment after several minutes. The neurological examination revealed intact cranial nerves with normal speech. There was a slight decrease in right upper and lower extremity strength. Sensory and cerebellar examinations were normal and the reflexes were all 2 + and symmetrical. The remainder of his physical examination was normal. Laboratory investigation revealed a normal complete blood count; serum Na+, 129 mEq/L; K+, 4.6 mEq/L; Cl-, 95 mEq/L; CO,, 27 mEq/L; BUN, 17 mg/dL. The serum glucose was 1030 mg/dL. The calculated serum osmolarity was 330 mOsm. Serum ketones were negative, and the urinalysis was normal except for 3+ glucose. The arterial pH was 7.42. Serum and urine toxicologic studies were negative. His hyperglycemia was controlled with diet, intravenous fluids, and glyburide 5 mg PO daily. The patient had no further abnormal motor activity following his admission, and his right-sided weakness
Clark A. Morres and Daniel J. Dire
resolved. A cranial computed tomography (CT scan), electroencephalogram (EEG), and lumbar puncture were all normal. The patient was discharged from the hospital on a maintenance dose of glyburide. The final diagnoses, reached after consultation with the neurology service, were 1) “Adult onset diabetes mellitus, noninsulin dependent ,” and 2) “Noncortical muscle contraction, secondary to wide swings in serum glucose.”
CASE 2 A 55-year-old hispanic male had hypertension for 8 years and was well controlled on captopril. He had been in excellent health with no history of diabetes or seizures when he presented for a complaint of shaking in his right arm. This occurred twice during the several hours prior to admission, with each episode lasting 1 to 2 minutes. The shaking began distally and progressed proximally to the shoulder, became increasingly violent, then subsided spontaneously. A review of systems revealed polyuria and polydipsia 3 months earlier, but his symptoms had waned until returning approximately one week prior to this presentation. On admission, no jerking or shaking movements were noted. The physical examination revealed a mildly obese male who was alert and oriented. Blood pressure was 182/100 mm Hg; pulse, 88 per minute, and temperature 37.2”C (98.9”F). The neurological examination revealed intact cranial nerves with normal speech. Motor, sensory, and cerebellar examinations were normal with the exception of slightly decreased deep tendon reflexes in the right upper and lower extremities. The remainder of his physical examination was normal. Laboratory investigation revealed a normal complete blood count, serum Na+, 131 mEq/L; K+, 4.0 mEq/L; CL-, 86 mEq/L; CO,, 31 mEq/L; BUN, 4 mg/dL. The serum glucose was 808 mg/dL. The calculated serum osmolarity was 315.3 mOsm. There were no ketones detected in the serum, and the urinalysis was normal except for 4+ glucose. The arterial pH was 7.48. His serum glucose decreased steadily with diet control and subcutaneous NPH insulin. No further abnormal motor activity was noted following admission, and his right-sided hyporeflexia resolved. A cranial CT scan and an EEG were normal. The patient was discharged on captopril 25 mg TID, hydrochlorothiazide 50 mg daily, and NPH insulin 24 units every morning. His final diagnoses following consultation with the neurology service were 1) “Adult onset
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diabetes,” 2) “Hypertension well controlled,” and 3) “Paroxysmal choreoathetosis/dystonica probably secondary to diabetes.”
DISCUSSION The syndrome of nonketotic hyperglycemia is commonly described in standard textbooks of emergency medicine (6,7). The clinical features mentioned include a variety of neurologic abnormalities including hemisensory deficits, hemianopsia, central pyrexia, visual hallucinations, and a wide variety of movement disorders (Table 1). Neurologists have shown a growing appreciation of focal seizures as the chief initial presenting sign of NKH (8,9), a condition that carries up to a 40% to 60% mortality if it progresses to hyperosmolar coma (5,6,9,10). The extent to which focal motor abnormalities occur and the variety of movement disorders that can result from this metabolic disturbance may be inadvertently minimized by the emergency physician. It is crucial that the emergency physician, as the primary care provider, become familiar with the variety of movement disorders that signal the presentation of this entity. This is especially true where cost containment considerations force greater reliance on the history and physical examination to suggest a diagnosis. For example, Eisner et. al. (11) examined the efficacy of a standard seizure workup in the ED and concluded that the standard laboratory diagnostic work-up used in evaluating seizure patients was not cost effective. They noted that, of 104 patients presenting with seizures and laboratory abnormalities, clinical examination successfully predicted the abnormalities in 102 patients. Hyperglycemia was one of the two abnormalities not predicted by history and physical examination. Familiarity with the movement disorders found in hyperglycemia may provoke the
Table 1. Movement Disorders Reported in NKH (2,4,6-9,20-24) Generalized seizures Focal seizures Todd’s paralysis Hemiparesis Myoclonus Tonic eye deviation Nystagmus Opsoclonus Hypereflexia Hyporeflexia Choreoathetosis Ballism Nuchal rigidity
use of inexpensive screening of NKH in patients presenting with complaints of seemingly bizarre and unusual movement disorders. Nonketotic hyperglycemic coma was first recognized in 1881 by Dreschfeld (12). He classified the cases of diabetic coma into three groups and described the associated movement disorders as follows: Convulsions are rarely noticed, and in the sixteen cases of my own, they occurred only once, and I find them noticed in six other cases, though jactation of the limbs is more common. A number of “diabetic coma” reports appeared in the medical literature through the 1920s to 1940s (1315). The modern concept of nonketotic hyperglycemia is most widely attributed to the 1957 report by Sament and Schwartz (16). The focal neurologic manifestations of this disorder began to gain increasing attention through the 1960s and 1970s. In the first extended discussion of focal seizures and an association with hyperglycemia, Maccario, Messis, and Vastola (4) reviewed eight cases of focal seizures in hyperglycemia. The movement disorders he reported were described as focal seizures or convulsions involving only one side of the body. Three of these patients showed posturing with head and eye deviation. Others had varying degrees of aphasia. In one patient, the abnormal movements were described as “shaking of her left arm and leg and twitching of the left side of her face” and, in another patient, as “clonic focal seizures involving the left extremities.” In these first reported cases, most of the patients were older than 60 years and 4 of 8 had no prior history of diabetes. Most had a loss of conciousness, although two patients described “shaking” of their extremities just as in the cases we presented. Most of the patients demonstrated transitory postictal signs including aphasia, homonymous hemianopsia, hemiparesis, hemihypalgesia, and reflex asymmetry. Our patient in case 2 also demonstrated a transitory reflex asymmetry. Maccario’s patients had little or no evidence of structural brain disease, and their seizures responded poorly to anticonvulsant therapy (phenytoin). Correction of the underlying metabolic disturbance prevented further seizurelike activity. Several subsequent reports have described the resistance of hyperglycemic seizures to anticonvulsive drug therapy and have noted that the use of phenytoin may actually be detrimental by depressing insulin release leading to increased hyperglycemia (2,9,17-19). These seizures are responsive to correction of the underlying metabolic disturbance with intravenous fluids alone or in
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concert with insulin (4). In cases where no organic structural lesions are found, the movement disorder usually does not return. Case reports and reviews from 1965 through 1986 (8,9,20-24) confirmed many of Maccario’s observations and further elucidated the clinical manifestations of patients with movement disorders and NKH. It is now recognized that motor seizures may be seen in up to 25% of patients with NKH (22-24). Focal motor seizures-defined as distinct clonic activity of the extremities, in some cases associated with posturing or aphasia-predominate 70% to 85% of the time. Berkovic, Johns, and Bladin (2) noted that the seizure content was remarkably similar in many reports about focal seizures in metabolic disorders. This is described as “tonic posturing on one side of the body with or without clonic jerking and speech arrest .” An ever-increasing variety of movement disorders have been reported in association with NKH in addition to what are commonly called focal motor seizures. In 1968, Maccario (20) reviewed the existing literature and reported on the neurologic dysfunction associated with hyperglycemia. The movement disorders noted in his review include aphasia, hemiparesis, focal and generalized tonic-clonic seizures, abnormal muscle tone (usually decreased but also rare intermittent stiffness of extremities), tonic eye deviation, nystagmus, and nuchal rigidity. Myoclonic twitches were described in patients in 1966 by Halmos, Nelson, and Lowry (25) as well as by Maccario (20). Mahon, Holland, and Urowitz (26) were the first to report a “prominent flapping tremor of the hands and the upper limbs” in association with NKH. He likened this tremor to the asterixis associated with hepatic coma. Singh, Gupta, and Strobos (22) described repetitive focal motor convulsions or epilepsia partialis continua (EPC) in 5 patients and reviewed 10 others in association with NKH in their initial 1973 report. All of his patients, unlike many of the previously reported cases, were conscious during these attacks and had extended episodes of continuous focal seizures persisting for an average of 6 days. This is much greater than in the two patients whom we present, whose movement disorders resolved spontaneously after several minutes but recurred. Additionally, the movement disorders in our patients had been present less than 12 hours at the time of their initial presentations. Singh described a variety of abnormal movements: “clonic contractions of quadriceps, aphasia, twitching of the right quadriceps, jerking of left arm and face, left arm twitching, right hand involuntary movements, twitching of arms and most commonly EPC of flexors.” Singh and Strobos (23) subsequently
Clark A. Morres and Daniel J. Dire
reported on 21 patients with EPC in association with NKH. He defined EPC as “repetitive, nonspreading, clonic muscular twitchings affecting a limited part of the body in a continuous fashion and lasting from several hours to several days.” In 1980, Abdias and Gabor (27) described the occurrence of focal motor seizures induced by movement in patients with nonketotic hyperglycemia. Unlike the movement-induced focal motor disorder described in our first patient, Abdias and Gabor noted that the seizures in their patients occurred “after sustained repetitive movements of a restricted area of the body.” The first patient whom we described developed abnormal movement following a single, sudden movement, more like those described by Kertesz (28) in his discussion of paroxysmal kinetogenic choreoathetosis (PKC). Kertesz asserted that the athetoid, tonic movements and posturing that occur in the presence of an “undisturbed consciousness” distinguish paroxysmal choreoathetoid movements from focal or central epilepsy. The descriptions of movement disorders in NKH that reveal posturing movements in the presence of undisturbed consciousness are strikingly similar to the movements of PKC described by Kertesz. Myoclonus and opsoclonia occurring simultaneously in patients with NKH have been described (29,30). These case reports described patients with eye movements characterized as “multidirectional rapid jerks” or “rapid irregular and chaotic.” The opsoclonic nature of the eye movements were confirmed by electronystagmography in one patient (29). These reports also described myoclonic irregular muscle jerks in the face and limbs in association with hyperglycemia (plasma glucose of 1,400 mg/dL and 827 mg/dL, respectively. Among the most recent and most elegant descriptions of the focal motor disorders seen in nonketotic hyperglycemia of diabetes mellitus is the 1981 report by Venna and Sabin (24). Their precise descriptions of the movement abnormalities seen in three patients with blood glucose ranging from 480 to 584 mg/dL illustrate well the variety of presentations likely to be encountered. These authors noted that the abnormal movements are often unknowingly described as “bizarre movements, ” “choreoathetosis,” or “hysterical seizures,” and are not recognized as seizures. Venna and Sabin described the “focal seizure” in one case as follows: Each episode began with the left hand groping about and clutching at the bedsheet. A few seconds later, the left arm was slowly abducted and extended at the shoulder, with the elbow half flexed and the hand
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clenched. As the arm began to be elevated the patient would attempt to hold it down with the right hand. The head and eyes would then slowly turn to the left and face the uplifted arm. In some instances the legs were held extended and the right arm was slightly abducted at the shoulder. Toward the end of the episode, clonic twitches appeared in the left hand for a few seconds. The patient seemed to be awake but was
unable to speak or utter any sounds. The entire sequence lasted one to three minutes. The descriptions of the “focal seizures” in their other two cases were described in similar detail, and depicted posturing, aphasia, myoclonic jerking movements and some irregular clonic movements. They regarded their patients’ clinical pictures as similar to other reported cases. A unique aspect of these cases was the posturing characteristic of the seizures that were labeled “fencing seizures” due to the appearance of the patient assuming a fencing stance. Movement-induced myoclonic jerking most accurately describes our first patient in this report. This appears to be the first reported case of movementinduced myoclonus in NKH following a single, sudden movement. However, Maccario previously raised this possibility (20) and provided the following explanation: The abnormal movements that can be present in these patients may have their origin at multiple levels of the neuroaxis. Thus, in certain cases the jerks seem to be intensified by voluntary movements and resemble “intention myoclonus.” Kertesz (28) and other authors have described maneuvers that patients with PKC have used to abort these abnormal movements. The “holding tight” maneuver or the “stopping still” maneuver used to abort PKC may explain how our patient was able to stop shaking when ordered to “stand at attention.” The likelihood that a patient, such as in our first case, would be able to induce focal motor abnormalities by voluntary movement as well as to abort them by the maneuvers mentioned by Kertesz seems small. Distinguishing voluntary from involuntary muscle jerking or twitching in such an instance would seem virtually impossible. However, we must postulate that our patient had the ability to initiate and terminate motor seizures without having intermediate voluntary control. A biochemical explanation may be based on the patient’s NKH. On the other hand, the mechanism of the patient’s abnormal movements may be entirely related to a functional disorder such as pseudoseizure. This latter explanation is equally unlikely if the diagnosis of entities such seizure must be made in the absence
as pseudoof organic
lesions. Although the patient we presented had no radiographic or electroencephalographic abnormalities, he certainly had a profound metabolic disturbance. We believe these two cases add to the variety of movement disorders that have been previously reported in NKH and widen the spectrum of possible presentations of hyperglycemia. In contrast to the reported ages of patients whose diabetes mellitus presented de novo with movement disorders as the chief initial manifestation (9,23), we note its occurrence in a patient as young as 26 years. The serum glucose level has been reported to range from 321 to 4800 mg/dL in NKH (4,23). In patients with normal mental status it is usually, but not always, less than 600 mg/dL (9,23). Alteration or loss of consciousness is felt to parallel the patient’s biochemical profile, and to decrease with increasing hyperglycemia, osmolality, serum sodium, and with decreasing fluid intake and serum carbon dioxide (6,10,20,23). Both patients whom we present exhibited movement disorders, not altered mentation, as their presenting complaint-in spite of having serum glucose levels above 800 mg/dL . Although the occurrence of movement-induced myoclonus has been alluded to in prior reports (20) we have noted it in association with NKH occurring after a single movement rather than after repetitive movements. Furthermore, we believe the rare occurrence of an abortive maneuver as described for choreoathetoid motor disturbances (“holding tight” phenomenon) is reported for the first time in association with a movement disorder in NKH.
SUMMARY Although nonketotic hyperglycemia commonly occurs in patients over 30 years of age, and one often sees depressed sensorium in patients whose serum glucose is greater than 800 mg/dL, we present two cases of unusual focal motor complaints in patients who were fully alert and oriented, one of whom was 26 years of age. In NKH, any of a variety of unusual motor complaints may be experienced by patients without evidence of any other disease process. The movement disorders associated with NHK usually resolve with correction of the underlying metabolic abnormalities. For the emergency physician, who at times must initiate therapy without a complete data base, it is particularly important to recall the wide variety of motor disturbances that can occur because of NKH and other metabolic disorders. It is also important to
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remember that patients with seizurelike movements may deteriorate if the diagnosis of nonketotic hyperglycemia is not recognized and treatment with anticonvulsants is initiated. Sorting out the “bizarre behaviors” and “hysterical seizures” from the movement disorders associated with metabolic disturbances by
clinical examination may be difficult in the busy ED. It may be helpful to utilize inexpensive, simple investigations such as urine dip sticks or blood glucose reagent strips to rule out the diagnosis of nonketotic hyperglycemia before it progresses to hyperosmolar coma with its subsequent high mortality.
REFERENCES 1. Plum F, Posner JB. The diagnosis of stupor and coma. Philadelphia: FA Davis; 1980:177-303. 2. Berkovic SF. Johns JA. Bladin PF. Focal seizures and svstemic metabolic disorders. Aust NZ J Med. 1982;12:620-3. I 3. Satran R, Griggs RC. Metabolic encephalopathy. In: Tyler HR, Dawson DM, eds. Current neurology. Vol 2. Boston: Houghton Mifflin; 1979:474-505. 4. Maccario M, Messis CP, Vastola EF. Focal seizures as a manifestation of hyperglycemia without ketoacidosis. Neurology. 1965;15:195-206. 5. Danowski TS. Non-ketotic coma and diabetes mellitus. Med Clin North Am. 1974;55:913-18. 6. Ragland G. Nonketotic hyperosmolar coma. In: Tintinalli JE, Krone RL, Ruiz E, ed. Emergency medicine: a comprehensive study guide. 2nd ed. New York: McGraw-Hill; 1988:504-8. 7. Graber TW. Diabetes. In: Rosen P, Baker FJ, Barkin RM, Braen R, Dailey R, Levy R, eds. Emergency medicine concepts and clinical practice. 2nd ed. St. Louis: CV Mosby Company; 1988:2039-63. 8. Askenasy JJ, Streifler M, Carasso R. Moderate nonketotic hyperglycemia-a cause of focal epilepsy. Eur Neurol. 1977;16: 51-61. 9. Messing RO, Simon RP. Seizures as a manifestation of systemic disease. Neurol Clin. 1986;4:563-84. 10. Arieff AI, Carroll HJ. Nonketotic hyperosmolar coma with hyperglycemia: clinical features, pathology, renal function, acid-base balance, plasma-cerebrospinal fluid equilibria and the effects of therapy in 37 cases. Medicine. 1972;51:73-94. 11. Eisner FR, Tbrnbull TL, Howes DS, Gold IW. Efficacy of a “standard” seizure workup in the emergency department. Ann Emerg Med. 1986;15:33-9. 12. Dreschfeld J. The Bradshaw Lecture on diabetic coma. Br Med J. 1886;2:358. 13. Warburg E. Some cases of diabetic coma complicated with uremia, and some remarks on the previous history of the diabetic coma. Acta Med Stand. 1925;61:301. 14. Salomonsen L, Harboe M. Renal insufficiency in coma diabeticurn. Acta Med Stand. 1926;63:425. 15. Root HF, Leech R. Diabetic coma and hyperglycemic stupor
compared. Med Clin North Am. 1946;30:1115. 16. Sament S, Schwartz MB. Severe diabetic stupor without ketosis. S Afr Med J. 1957;31:893. 17. Malherbe C, Burril KC, Levin SR, Karam JH, Forsham PH. Effect of diphenylhydantoin on insulin secretion in man. N Engl J Med. 1972;286:339-42. 18. Goldberg ME. Sanbar SS. Hvoerelvcemic. nonketotic coma following administration of Dii&in idiphenylhydantoin). Diabetes. 1969;18:101-6. 19. Klein JP. Diphenylhydantoin intoxication associated with hyperglycemia. Pediatr Pharmacol Therap. 1966;69:463-5. 20. Maccario M. Neurological dysfunction associated with nonketotic hyperglycemia. Arch Neurol. 1968;19:525-34. 21. Daniels JC, Chokroverty S, Barron KD. Anacidotic hyperglycemia and focal seizures. Arch Intern Med. 1%9;124:701-6. 22. Singh BM, Gupta DR, Strobos RJ. Nonketotic hyperglycemia and epilepsia partialis continua. Arch Neurol. 1973;29:18790. 23. Singh BM, Strobos RJ. Epilepsia partialis continua associated with nonketotic hyperglycemia: clinical and biochemical profile of 21 patients. Ann Neurol. 1980;8:155-60. 24. Venna N, Sabin TD. Tonic focal seizures in nonketotic hyperglycemia of diabetes mellitus. Arch Neurol. 1981;38:51214. 25. Halmos PB, Nelson JK, Lowry RC. Hyperosmolar non-ketoacidotic coma in diabetes. Lancet. 1966; 1:675-9. 26. Mahon WA, Holland J, Urowitz MB. Hyperosmolar, non-ketotic diabetic coma. Can Med Assoc J. 1968;99:1090-2. 27. Abdias A, Gabor AJ. Movement-induced seizures in nonketotic hyperglycemia. Neurology. 1980;30:600-4. 28. Kertesz A. Paroxysmal kinesigenic choreoathetosis. Neurology. 1967;17:680-90. 29. Matsumura K, Sonoh M, Tamaoka A, Sakuta M. Syndrome of opsoclonus-myoclonus in hyperosmolar nonketotic coma. Ann Neurol. 1985;18:623-4. 30. Noda, S, Takao A, Itoh H, Umezaki H. Opsoclonus in hyperosmolar nonketotic coma. J Neurol Neurosurg Psychiatry. 1985;48:1186.
Printed In the USA
1989
MOVEMENT DISORDERS AS A MANIFESTATION OF NONKETOTIC HYPERGLYCEMIA Clark A. Morres,
MD,
Cpt., MC, USA, and Daniel J. Dire, MD,Cpt., MC, USA
Department of Emergency
Medicine, Emergency Medicine Residency Program, Darnall Army Community Hospital, Ft. Hood, Texas 76544-5063 Reprint address: Daniel J. Dire, MD, Cpt., MC, Department of Emergency Medicine, Darnall Army Hospital, Ft. Hood, TX 76544-5063
0 Abstract - Movement disorders are well-known presenting signs of metabolic disorders. Focal motor abnormalities may be the chief initial presentation of diabetes mellitus in the nonketotic hyperglycemic state in 6% of patients. Nonketotic hyperglycemia (NKH), in particular, may manifest any of a wide variety of movement disorders. These have been described as focal seizures, epllepsia partialis continua, myoclonus, and opsoclonia. There are descriptions of movement disorders in hyperglycemia that are similar to the coarse flapping tremor of asterlxls, the posturing of paroxysmal kinetogenic choreoathetosis, and of “fencing (stance) seizures.” Disorders of facial motor function including aphasia, facial muscle twitching and jerking, and disorders of muscular tone have been described. These may include hemiparesis and hemiplegias as well as increased tone, in some cases mimicking the nuchal rigidity of meningitis. The movement disorders in NKH may mimic cerebral vascular accidents, meningitis, or psychiatric disorders, as well as various types of seizures. Clinicians may be able to avoid expensive and time-consuming diagnostic evaluations to rule out NKH in patients with movement disorders. We present two patients with focal motor abnormalities associated with nonketonic hyperglycemia and review the pertinent literature.
of movement disorders are known manifestations of metabolic disorders including hepatic encephalopathy, hyponatremia, hypocalcemia, uremia, and hypoxia (l-3). Hyperglycemia is the most common metabolic disturbance that can result in focal motor seizures and other focal motor phenomena (2,4). Numerous reports in the neurological literature and more rare reports in the general medical literature draw attention to the importance of this entity (2). These reports also depict a wide variation in the kinds of motor disturbances observed. Although disorders of movement alone can be the presenting sign of diabetes mellitus, no reports or reviews of this clinical manifestation of nonketotic hyperglycemia (NKH) appear in the emergency medicine literature. The importance of recognizing these movement disorders is crucial since mortality is as high as 40% to 60% when hyperglycemia progresses to hyperosmolar coma (596).
• I Keywords-movement disorders; focal seizures; nonketotic hyperglycemia; seizures; hyperglycemia
A 26-year-old black male who was in excellent health with no history of diabetes or seizures was evaluated in the emergency department (ED) three separate times over a 30-hour period for a complaint of shaking in his right arm and right leg. At his first presentation, the patient stated that the shaking had begun spontaneously while he was in his sleeping bag outdoors on the ground during a cold night. The shaking subsided spontaneously after several minutes but recurred the next morning, prompting him to seek medical treatment in the ED. The shaking had subsided prior to evaluation and thus was not witnessed. The patient’s physical examination was normal. He
INTRODUCTION
Neurologic abnormalities
that include a wide range
The opinions or assertions contained herein are those of the authors and should not be construed as official or representing the opinions of the Department of the Army or the Department of Defense.
CASE 1
RECEIVED:12 April 1988; FINALSUBMISSION RECEIVED:6 December ACCEPTED: 13 December 1988
1988;
0736-4679/89 $3.00 + .OO
360
was discharged with a diagnosis of “nonspecific muscle contractions,” possibly related to the cold ambient temperatures. The patient returned to the ED 22 hours later with the same complaints. While being evaluated, he was asked to move his right leg. This precipitated a shaking episode resembling myoclonic muscle contractions that was thought by the examining physician to be under voluntary control. The remainder of the physical examination was normal. There was no positive Babinski sign, and deep tendon reflexes were normal even during the shaking episode. The patient had several similar episodes while in the ED, lasting from 20 seconds to 2 minutes. The patient’s shaking stopped immediately when he was ordered to stand at attention by a superior officer. Several psychosocial stresses were identified after interviewing co-workers and supervisors to include a pending disciplinary action for drug abuse, personality disputes, and lack of military bearing. The patient was discharged with the diagnosis of “possible pseudoseizure” perhaps related to an antisocial personality disorder. Follow-up consultations with the community mental health department and social work department were arranged. The patient presented to the ED for a third time, again with shaking and jerking movements of the right leg and right arm lasting 5 to 10 minutes at a time. He had now developed polyuria and polydipsia. He had been incontinent of urine just prior to arrival. The physical examination revealed an alert, oriented black male. Vital signs were blood pressure, 142/90 mm Hg; pulse, 88 per minute; and temperature, 35.2”C (95.3”F). The patient was noted to have a shaking in the right arm and leg. These movements subsided without treatment after several minutes. The neurological examination revealed intact cranial nerves with normal speech. There was a slight decrease in right upper and lower extremity strength. Sensory and cerebellar examinations were normal and the reflexes were all 2 + and symmetrical. The remainder of his physical examination was normal. Laboratory investigation revealed a normal complete blood count; serum Na+, 129 mEq/L; K+, 4.6 mEq/L; Cl-, 95 mEq/L; CO,, 27 mEq/L; BUN, 17 mg/dL. The serum glucose was 1030 mg/dL. The calculated serum osmolarity was 330 mOsm. Serum ketones were negative, and the urinalysis was normal except for 3+ glucose. The arterial pH was 7.42. Serum and urine toxicologic studies were negative. His hyperglycemia was controlled with diet, intravenous fluids, and glyburide 5 mg PO daily. The patient had no further abnormal motor activity following his admission, and his right-sided weakness
Clark A. Morres and Daniel J. Dire
resolved. A cranial computed tomography (CT scan), electroencephalogram (EEG), and lumbar puncture were all normal. The patient was discharged from the hospital on a maintenance dose of glyburide. The final diagnoses, reached after consultation with the neurology service, were 1) “Adult onset diabetes mellitus, noninsulin dependent ,” and 2) “Noncortical muscle contraction, secondary to wide swings in serum glucose.”
CASE 2 A 55-year-old hispanic male had hypertension for 8 years and was well controlled on captopril. He had been in excellent health with no history of diabetes or seizures when he presented for a complaint of shaking in his right arm. This occurred twice during the several hours prior to admission, with each episode lasting 1 to 2 minutes. The shaking began distally and progressed proximally to the shoulder, became increasingly violent, then subsided spontaneously. A review of systems revealed polyuria and polydipsia 3 months earlier, but his symptoms had waned until returning approximately one week prior to this presentation. On admission, no jerking or shaking movements were noted. The physical examination revealed a mildly obese male who was alert and oriented. Blood pressure was 182/100 mm Hg; pulse, 88 per minute, and temperature 37.2”C (98.9”F). The neurological examination revealed intact cranial nerves with normal speech. Motor, sensory, and cerebellar examinations were normal with the exception of slightly decreased deep tendon reflexes in the right upper and lower extremities. The remainder of his physical examination was normal. Laboratory investigation revealed a normal complete blood count, serum Na+, 131 mEq/L; K+, 4.0 mEq/L; CL-, 86 mEq/L; CO,, 31 mEq/L; BUN, 4 mg/dL. The serum glucose was 808 mg/dL. The calculated serum osmolarity was 315.3 mOsm. There were no ketones detected in the serum, and the urinalysis was normal except for 4+ glucose. The arterial pH was 7.48. His serum glucose decreased steadily with diet control and subcutaneous NPH insulin. No further abnormal motor activity was noted following admission, and his right-sided hyporeflexia resolved. A cranial CT scan and an EEG were normal. The patient was discharged on captopril 25 mg TID, hydrochlorothiazide 50 mg daily, and NPH insulin 24 units every morning. His final diagnoses following consultation with the neurology service were 1) “Adult onset
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diabetes,” 2) “Hypertension well controlled,” and 3) “Paroxysmal choreoathetosis/dystonica probably secondary to diabetes.”
DISCUSSION The syndrome of nonketotic hyperglycemia is commonly described in standard textbooks of emergency medicine (6,7). The clinical features mentioned include a variety of neurologic abnormalities including hemisensory deficits, hemianopsia, central pyrexia, visual hallucinations, and a wide variety of movement disorders (Table 1). Neurologists have shown a growing appreciation of focal seizures as the chief initial presenting sign of NKH (8,9), a condition that carries up to a 40% to 60% mortality if it progresses to hyperosmolar coma (5,6,9,10). The extent to which focal motor abnormalities occur and the variety of movement disorders that can result from this metabolic disturbance may be inadvertently minimized by the emergency physician. It is crucial that the emergency physician, as the primary care provider, become familiar with the variety of movement disorders that signal the presentation of this entity. This is especially true where cost containment considerations force greater reliance on the history and physical examination to suggest a diagnosis. For example, Eisner et. al. (11) examined the efficacy of a standard seizure workup in the ED and concluded that the standard laboratory diagnostic work-up used in evaluating seizure patients was not cost effective. They noted that, of 104 patients presenting with seizures and laboratory abnormalities, clinical examination successfully predicted the abnormalities in 102 patients. Hyperglycemia was one of the two abnormalities not predicted by history and physical examination. Familiarity with the movement disorders found in hyperglycemia may provoke the
Table 1. Movement Disorders Reported in NKH (2,4,6-9,20-24) Generalized seizures Focal seizures Todd’s paralysis Hemiparesis Myoclonus Tonic eye deviation Nystagmus Opsoclonus Hypereflexia Hyporeflexia Choreoathetosis Ballism Nuchal rigidity
use of inexpensive screening of NKH in patients presenting with complaints of seemingly bizarre and unusual movement disorders. Nonketotic hyperglycemic coma was first recognized in 1881 by Dreschfeld (12). He classified the cases of diabetic coma into three groups and described the associated movement disorders as follows: Convulsions are rarely noticed, and in the sixteen cases of my own, they occurred only once, and I find them noticed in six other cases, though jactation of the limbs is more common. A number of “diabetic coma” reports appeared in the medical literature through the 1920s to 1940s (1315). The modern concept of nonketotic hyperglycemia is most widely attributed to the 1957 report by Sament and Schwartz (16). The focal neurologic manifestations of this disorder began to gain increasing attention through the 1960s and 1970s. In the first extended discussion of focal seizures and an association with hyperglycemia, Maccario, Messis, and Vastola (4) reviewed eight cases of focal seizures in hyperglycemia. The movement disorders he reported were described as focal seizures or convulsions involving only one side of the body. Three of these patients showed posturing with head and eye deviation. Others had varying degrees of aphasia. In one patient, the abnormal movements were described as “shaking of her left arm and leg and twitching of the left side of her face” and, in another patient, as “clonic focal seizures involving the left extremities.” In these first reported cases, most of the patients were older than 60 years and 4 of 8 had no prior history of diabetes. Most had a loss of conciousness, although two patients described “shaking” of their extremities just as in the cases we presented. Most of the patients demonstrated transitory postictal signs including aphasia, homonymous hemianopsia, hemiparesis, hemihypalgesia, and reflex asymmetry. Our patient in case 2 also demonstrated a transitory reflex asymmetry. Maccario’s patients had little or no evidence of structural brain disease, and their seizures responded poorly to anticonvulsant therapy (phenytoin). Correction of the underlying metabolic disturbance prevented further seizurelike activity. Several subsequent reports have described the resistance of hyperglycemic seizures to anticonvulsive drug therapy and have noted that the use of phenytoin may actually be detrimental by depressing insulin release leading to increased hyperglycemia (2,9,17-19). These seizures are responsive to correction of the underlying metabolic disturbance with intravenous fluids alone or in
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concert with insulin (4). In cases where no organic structural lesions are found, the movement disorder usually does not return. Case reports and reviews from 1965 through 1986 (8,9,20-24) confirmed many of Maccario’s observations and further elucidated the clinical manifestations of patients with movement disorders and NKH. It is now recognized that motor seizures may be seen in up to 25% of patients with NKH (22-24). Focal motor seizures-defined as distinct clonic activity of the extremities, in some cases associated with posturing or aphasia-predominate 70% to 85% of the time. Berkovic, Johns, and Bladin (2) noted that the seizure content was remarkably similar in many reports about focal seizures in metabolic disorders. This is described as “tonic posturing on one side of the body with or without clonic jerking and speech arrest .” An ever-increasing variety of movement disorders have been reported in association with NKH in addition to what are commonly called focal motor seizures. In 1968, Maccario (20) reviewed the existing literature and reported on the neurologic dysfunction associated with hyperglycemia. The movement disorders noted in his review include aphasia, hemiparesis, focal and generalized tonic-clonic seizures, abnormal muscle tone (usually decreased but also rare intermittent stiffness of extremities), tonic eye deviation, nystagmus, and nuchal rigidity. Myoclonic twitches were described in patients in 1966 by Halmos, Nelson, and Lowry (25) as well as by Maccario (20). Mahon, Holland, and Urowitz (26) were the first to report a “prominent flapping tremor of the hands and the upper limbs” in association with NKH. He likened this tremor to the asterixis associated with hepatic coma. Singh, Gupta, and Strobos (22) described repetitive focal motor convulsions or epilepsia partialis continua (EPC) in 5 patients and reviewed 10 others in association with NKH in their initial 1973 report. All of his patients, unlike many of the previously reported cases, were conscious during these attacks and had extended episodes of continuous focal seizures persisting for an average of 6 days. This is much greater than in the two patients whom we present, whose movement disorders resolved spontaneously after several minutes but recurred. Additionally, the movement disorders in our patients had been present less than 12 hours at the time of their initial presentations. Singh described a variety of abnormal movements: “clonic contractions of quadriceps, aphasia, twitching of the right quadriceps, jerking of left arm and face, left arm twitching, right hand involuntary movements, twitching of arms and most commonly EPC of flexors.” Singh and Strobos (23) subsequently
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reported on 21 patients with EPC in association with NKH. He defined EPC as “repetitive, nonspreading, clonic muscular twitchings affecting a limited part of the body in a continuous fashion and lasting from several hours to several days.” In 1980, Abdias and Gabor (27) described the occurrence of focal motor seizures induced by movement in patients with nonketotic hyperglycemia. Unlike the movement-induced focal motor disorder described in our first patient, Abdias and Gabor noted that the seizures in their patients occurred “after sustained repetitive movements of a restricted area of the body.” The first patient whom we described developed abnormal movement following a single, sudden movement, more like those described by Kertesz (28) in his discussion of paroxysmal kinetogenic choreoathetosis (PKC). Kertesz asserted that the athetoid, tonic movements and posturing that occur in the presence of an “undisturbed consciousness” distinguish paroxysmal choreoathetoid movements from focal or central epilepsy. The descriptions of movement disorders in NKH that reveal posturing movements in the presence of undisturbed consciousness are strikingly similar to the movements of PKC described by Kertesz. Myoclonus and opsoclonia occurring simultaneously in patients with NKH have been described (29,30). These case reports described patients with eye movements characterized as “multidirectional rapid jerks” or “rapid irregular and chaotic.” The opsoclonic nature of the eye movements were confirmed by electronystagmography in one patient (29). These reports also described myoclonic irregular muscle jerks in the face and limbs in association with hyperglycemia (plasma glucose of 1,400 mg/dL and 827 mg/dL, respectively. Among the most recent and most elegant descriptions of the focal motor disorders seen in nonketotic hyperglycemia of diabetes mellitus is the 1981 report by Venna and Sabin (24). Their precise descriptions of the movement abnormalities seen in three patients with blood glucose ranging from 480 to 584 mg/dL illustrate well the variety of presentations likely to be encountered. These authors noted that the abnormal movements are often unknowingly described as “bizarre movements, ” “choreoathetosis,” or “hysterical seizures,” and are not recognized as seizures. Venna and Sabin described the “focal seizure” in one case as follows: Each episode began with the left hand groping about and clutching at the bedsheet. A few seconds later, the left arm was slowly abducted and extended at the shoulder, with the elbow half flexed and the hand
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clenched. As the arm began to be elevated the patient would attempt to hold it down with the right hand. The head and eyes would then slowly turn to the left and face the uplifted arm. In some instances the legs were held extended and the right arm was slightly abducted at the shoulder. Toward the end of the episode, clonic twitches appeared in the left hand for a few seconds. The patient seemed to be awake but was
unable to speak or utter any sounds. The entire sequence lasted one to three minutes. The descriptions of the “focal seizures” in their other two cases were described in similar detail, and depicted posturing, aphasia, myoclonic jerking movements and some irregular clonic movements. They regarded their patients’ clinical pictures as similar to other reported cases. A unique aspect of these cases was the posturing characteristic of the seizures that were labeled “fencing seizures” due to the appearance of the patient assuming a fencing stance. Movement-induced myoclonic jerking most accurately describes our first patient in this report. This appears to be the first reported case of movementinduced myoclonus in NKH following a single, sudden movement. However, Maccario previously raised this possibility (20) and provided the following explanation: The abnormal movements that can be present in these patients may have their origin at multiple levels of the neuroaxis. Thus, in certain cases the jerks seem to be intensified by voluntary movements and resemble “intention myoclonus.” Kertesz (28) and other authors have described maneuvers that patients with PKC have used to abort these abnormal movements. The “holding tight” maneuver or the “stopping still” maneuver used to abort PKC may explain how our patient was able to stop shaking when ordered to “stand at attention.” The likelihood that a patient, such as in our first case, would be able to induce focal motor abnormalities by voluntary movement as well as to abort them by the maneuvers mentioned by Kertesz seems small. Distinguishing voluntary from involuntary muscle jerking or twitching in such an instance would seem virtually impossible. However, we must postulate that our patient had the ability to initiate and terminate motor seizures without having intermediate voluntary control. A biochemical explanation may be based on the patient’s NKH. On the other hand, the mechanism of the patient’s abnormal movements may be entirely related to a functional disorder such as pseudoseizure. This latter explanation is equally unlikely if the diagnosis of entities such seizure must be made in the absence
as pseudoof organic
lesions. Although the patient we presented had no radiographic or electroencephalographic abnormalities, he certainly had a profound metabolic disturbance. We believe these two cases add to the variety of movement disorders that have been previously reported in NKH and widen the spectrum of possible presentations of hyperglycemia. In contrast to the reported ages of patients whose diabetes mellitus presented de novo with movement disorders as the chief initial manifestation (9,23), we note its occurrence in a patient as young as 26 years. The serum glucose level has been reported to range from 321 to 4800 mg/dL in NKH (4,23). In patients with normal mental status it is usually, but not always, less than 600 mg/dL (9,23). Alteration or loss of consciousness is felt to parallel the patient’s biochemical profile, and to decrease with increasing hyperglycemia, osmolality, serum sodium, and with decreasing fluid intake and serum carbon dioxide (6,10,20,23). Both patients whom we present exhibited movement disorders, not altered mentation, as their presenting complaint-in spite of having serum glucose levels above 800 mg/dL . Although the occurrence of movement-induced myoclonus has been alluded to in prior reports (20) we have noted it in association with NKH occurring after a single movement rather than after repetitive movements. Furthermore, we believe the rare occurrence of an abortive maneuver as described for choreoathetoid motor disturbances (“holding tight” phenomenon) is reported for the first time in association with a movement disorder in NKH.
SUMMARY Although nonketotic hyperglycemia commonly occurs in patients over 30 years of age, and one often sees depressed sensorium in patients whose serum glucose is greater than 800 mg/dL, we present two cases of unusual focal motor complaints in patients who were fully alert and oriented, one of whom was 26 years of age. In NKH, any of a variety of unusual motor complaints may be experienced by patients without evidence of any other disease process. The movement disorders associated with NHK usually resolve with correction of the underlying metabolic abnormalities. For the emergency physician, who at times must initiate therapy without a complete data base, it is particularly important to recall the wide variety of motor disturbances that can occur because of NKH and other metabolic disorders. It is also important to
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remember that patients with seizurelike movements may deteriorate if the diagnosis of nonketotic hyperglycemia is not recognized and treatment with anticonvulsants is initiated. Sorting out the “bizarre behaviors” and “hysterical seizures” from the movement disorders associated with metabolic disturbances by
clinical examination may be difficult in the busy ED. It may be helpful to utilize inexpensive, simple investigations such as urine dip sticks or blood glucose reagent strips to rule out the diagnosis of nonketotic hyperglycemia before it progresses to hyperosmolar coma with its subsequent high mortality.
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