A 41-Year-Old Man With New Headache and Altered Mental Status

A 41-year-old man with a history of diet-controlled diabetes mellitus developed acute-onset confusion and mild holocephalic headache relieved by acetaminophen. His confusion worsened over the course of 5 days, and he was subsequently brought to his primary care physician by his family, where he was noted to have an altered mental status. He was admitted to a local hospital for evaluation. Magnetic resonance imaging (MRI) of the brain showed an area of restricted diffusion on diffusion-weighted imaging in the left temporal cortex, consistent with a subacute infarction. Diagnostic testing with lumbar puncture, computed tomography (CT) angiogram of the head and neck, transthoracic echocardiogram (TTE) without saline contrast bubble, fasting lipid analysis, hypercoagulability analysis, and routine laboratory analysis showed only a hemoglobin of 11.9 g/dL (ref 14.0-17.5 g/dL), an elevated creatine phosphokinase (CPK) at 510 U/L (ref 55-380 U/L), elevated postprandial glucose at 252 mg/dL, a low-density lipoprotein (LDL) cholesterol of 122 mg/dL (ref 1-100 mg/dL), and a high-density lipoprotein (HDL) cholesterol of 32 mg/dL (ref 40-85 mg/dL). The patient was diagnosed with a subacute ischemic stroke in the left temporal lobe, producing a Wernicke aphasia, and was discharged home on aspirin and pravastatin with primary care follow-up to better control his elevated blood glucose. Over the course of the next 9 months the patient was readmitted to the hospital 4 times for progressively worsening mental status, aggressive behaviors, right-hand side weakness, and seizures. Brain imaging on each admission showed progressive infarcts in multiple vascular territories (Figure 1 ). During this time, a transesophageal echocardiogram (TEE) with saline contrast bubble was performed, which showed flow across the interatrial septum with Valsalva maneuver, consistent with a small patent foramen ovale (PFO). However, lower extremity doppler ultrasound and MR venogram of the pelvis failed to show evidence of deep vein thrombosis. The patient was placed on aspirin and warfarin for presumed paradoxical embolus and transferred to this facility for further evaluation. Figure 1. Imaging of progressive multifocal infarcts. A, Noncontrast CT scan of the brain 10 days after initial presentation showing a focal area of encephalomalacia in the left temporal lobe, representing an old infarct as well as an area of low attenuation and . Other than impaired glucose tolerance, his medical history was significant only for hearing loss, requiring the use of hearing aids. The patient worked in a cannery until he became ill, with no known exposures to chemicals or infectious agents while at work or at home. He did not smoke tobacco, drink alcohol, or use illicit drugs. The patient's mother, father, and one of his brothers had diabetes. Of his 5 sisters, 4 had early miscarriages. His paternal aunt and first cousin both had a seizure disorder. On admission to this hospital, temperature was 36.8°C, blood pressure 107/61 mm Hg, pulse 103 beats/min, respiratory rate 18/min, and oxygen saturation 97% on room air. General physical examination showed a cachectic patient in no apparent distress, with anicteric sclerae, a clear oropharynx, a regular cardiac rhythm with normal s1 and s2 heart sounds, lungs clear to ascultation, a nontender and nondistended abdomen, urinary incontinence requiring a diaper, and ecchymosis on the right anterior shin. Neurologic examination showed an alert patient able to regard the examiner but oriented only to person, without dysarthria but speaking in 1- to 3-word sentences with perseveration and echolalia, unable to follow commands, normal cranial nerves, antigravity strength in all 4 extremites but favoring the left over the right, 3+ deep tendon reflexes throughout, with slightly brisker reflexes on the right-hand side compared to the left, withdrawal to pain in all 4 extremities, and a narrow but unsteady gait. A repeat MRI of the brain with and without contrast was unchanged from the most recent study performed at the referring hospital (Figure 1E). The patient was placed on telemetry monitoring. A repeat TEE with saline contrast bubble showed no evidence of right-to-left shunt, atrial or ventricular thrombus, or pathology within the aortic arch. A diagnostic cerebral angiogram was performed, which showed no evidence of atherosclerosis or vasculitis within the cerebral arteries. An extensive serum laboratory analysis was performed, the results of which are shown in Table 1 . Table 1. Serum Laboratory Testsa The patient underwent a repeat lumbar puncture. The cerebrospinal fluid (CSF) was clear and colorless, with 2 white blood cells and 650 red blood cells, glucose of 69 mg/dL (serum glucose 153 mg/dL), elevated protein at 89 mg/dL (ref 15-50 mg/dL), lactate dehydrogenase level of 15 U/L, elevated lactate at 6.5 mmol/L (ref 1.1-2.8 mmol/L), normal pyruvate, no oligoclonal bands present, and an elevated immunoglobulin G (IgG) index at 0.8 (ref 0.3-0.6). Polymerase chain reaction on the CSF for varicella zoster virus and herpes simplex 1 and 2 viruses was negative. Cerebrospinal fluid cryptococcal antigen, Borrelia burgdorferi antibodies, and venereal disease research laboratory (VDRL) test for syphilis were also negative. A diagnostic test was performed.