Cerebral Vascular Accident in the Infected Diabetic Ulcer Patient

To the Editor:

Cerebral vascular accidents are the third leading cause of death in the United States.[1] Over 550,000 Americans suffer from strokes each year, resulting in 150,000 fatalities.[2] Risk factors are identified as modifiable or nonmodifiable. Multiple modifiable risk factors are smoking, diabetes mellitus, atrial fibrillation, transient ischemic attacks, congestive heart failure, obesity, alcoholism, and hyperlipidemia. Nonmodifiable risk factors include increased age, male gender, heredity, and African-American ethnicity.[3,4] Cerebral vascular accidents are categorized into two groups: infarction and hemorrhage. Infarctions are caused by atherothrombic, embolic, and transient ischemic attacks. Hemorrhage types are caused by aneurysmal and intraparenchymal events.[1]

All three forms of infarction may be present and interact together in the infected diabetic patient. Of these, thrombotic causes of infarction constitute 45% of cerebral ischemia and cerebral vascular accidents.[1] This is especially prevalent in patients with diabetes due to an error in metabolism of lipids and the resultant hyperlipidemia that leads to atherosclerosis.[5] Thrombotic causes may also be related to hypercoagulated states, such as infection, inflammation, and coagulation disorders. Transient ischemic attacks should be viewed as a warning sign of potentially major thrombotic events. Transient ischemic attacks are defined as neurologic deficits of 1-hour duration. The most common symptoms are loss of balance, visual disturbances, sensory disturbances, aphasia, or headache. Embolic events are strongly suspected as the initiating event for a transient ischemic attack and are characterized by rapid, severe neurologic changes. They are most commonly related to a cardiac emboli.[1]

Cerebral vascular accidents that occur within 1 week of an infective process are associated with increased morbidity and mortality.[1] Infection changes the coagulation balance. Increased levels of fibrinogen, acute phase proteins, and leukocytes induce a hypercoagulable state that produces increased immune complexes, platelet aggregation, and blood viscosity.[6,7] Increased levels of fibrinogen have been inversely linked to cerebral blood flow and, thus, viscosity. Patients with infections will also have increased fibrin D-dimer levels and C-reactive proteins. Fibrin D-dimer levels provide the clinician with a rough estimate of coagulation activity and may be used as a screen.[8] However, since patients with diabetes have decreased fibrinolytic functioning, their fibrin D-dimer may not be as elevated as in patients without diabetes.[9] In this article, a cerebral vascular accident associated with a diabetic foot infection which was initially diagnosed as infection-associated encephalopathy is presented.

Case Report

A 77-year-old man with diabetes was admitted to the Southern Arizona Veterans Affairs Medical Center in Tucson, Arizona, for cellulitis and osteomyelitis of the right foot. The patient related a history of a 102° fever with accompanying chills for 2 days and reported only local wound care to the area by his primary care provider 2 weeks prior to admission. Significant medical history included chronic renal failure with only 20% remaining function, hyperlipidemia, macular degeneration, loss of vision, and coronary artery bypass graft surgery 3 years earlier. The physical examination was significant for visual deficiency and the following lower-extremity findings. Monophasic dorsalis pedis and palpable posterior tibial arteries were identified. Erythema and edema extended proximally on the right foot to the midfoot. An ulceration lateral-plantar over the fifth metatarsophalangeal joint measuring 2.5 cm × 1.5 cm that probed to bone was identified. Purulent drainage was noted. Significant admission laboratory data included an elevated creatinine of 3.4 mg/dL, blood urea nitrogen of 37 mg/dL, Westergren sedimentation rate of 73 mm/h, and neutrophil of 76.8%. The patient was started on Unasyn at a reduced dosage of 1.5 g every 12 hours based on pharmacy recommendations.

On the morning of his second hospital day, the patient reported that he had fallen in the bathroom. He denied physical injuries but reported a lingering sense of dizziness and confusion. The patient was examined and no physical injuries were noted. The patient answered all questions appropriately. Later that day, the patient’s neurologic status deteriorated rapidly. He developed aphasia, incontinence, loss of locomotion, and loss of controlled upper-extremity movements. Electrocardiograph studies revealed a rhythm change, but no ischemic damage, which was confirmed by laboratory troponin I values of less than 0.15 ng/mL. Serum chemistries remained similar to admission values; however, the white blood cell count increased from the admission level of 9,400 to 13,100 and the prothrombin time was abnormal at 15.7 seconds. Computed tomography (CT) of the head was negative for intracranial hemorrhage, mass, or edema. The consulting neurologist administered Narcan and Ativan to rule out narcotic toxicity and possible seizure disorder. There was no response to either medication. The neurologist diagnosed the patient as having encephalopathy secondary to systemic infection. A lumbar puncture was ordered for the next day. By late evening of the second day the patient had regained control of upper-extremity movements, was responding to commands, and could speak but not coherently. On the third hospital day a lumbar puncture was performed, which was negative for bacteria and cells. The neurologic deficits remained at the same level. A second CT was ordered, which indicated areas of possible right occipital infarction. On the fourth hospital day, the patient experienced a respiratory arrest and was transferred to the intensive care unit and intubated. The patient remained unresponsive and began decerebrate posturing. Magnetic resonance imaging (MRI) studies demonstrated multiple acute cerebral vascular accidents located in the brainstem and cerebellum. Imaging angiography revealed an occluded basilar artery and extensive atherosclerotic disease. A heparin bolus was given to the patient upon admission to the intensive care unit, but the patient experienced an acute gastrointestinal bleed. The heparin was then discontinued. Multiple laboratory studies indicated a metabolic acidosis and increasing blood urea nitrogen, creatinine, white blood cell count, and coagulation. The patient was maintained on the ventilator until the seventh hospital day when he died as a result of cardiovascular collapse.

Conclusion

Mental status changes in patients with diabetes are more commonly related to hyperglycemia or hypoglycemia, but the possibility of a stroke also must be considered. Patients with diabetes and acute infections are at a four times greater risk to experience a major cerebral vascular accident than a patient without diabetes.[3] Physical examination and re-examination of the patient for localization of symptoms and progression of neurologic deficits are important information for the neurologist. Potential risk factors must be identified early and appropriate initial laboratory tests conducted, including coagulation studies such as PT, aPTT, fibrinogen, and D-dimer. The immunologic component of C-reactive protein should also be followed. Imaging studies such as CT, MRI, and magnetic resonance angiography are important for diagnostic purposes. Early identification of transient ischemic attacks and cerebral vascular accidents allows the clinician to involve neurologic services early in their development.