Repeated brain MRI scans show four small gray matter lesions. What’s in your differential?
A 43-year-old woman had a convulsive episode when she was at work. She does not recall the episode, but a coworker described it to the paramedics when they arrived, and the patient has carefully looked at her own chart and followed up with her colleague to learn more about what happened.
It began with the patient shaking her left arm for a few seconds. Then the left side of her face started to droop, and she fell to the ground. Her whole body was shaking for a few seconds before she passed out.
She was taken to the emergency department (ED), where she was examined. In the ED, she was groggy, her left arm was weak, and her face was droopy. The results of a brain CT scan were abnormal, and she was admitted for a full evaluation. The left-sided face and arm weakness resolved after about 24 hours.
The patient received a diagnosis of lupus at age 35. Her symptoms are primarily related to joint pain. She had a recurrence of symptoms one year before this episode and was given a prescription for oral corticosteroids. After 6 months, the dose was tapered and then discontinued. Her joint symptoms have not recurred since then.
She appears well nourished, is in no acute distress, and is oriented and cooperative, with normal affect. No skin discoloration or lesions are evident, and the results of cardiac, respiratory, and abdominal examinations are normal.
Her extraocular movements are full and intact with no nystagmus or saccades. She does not have double vision, visual defects, or papilledema. Pupils are equal, round, and reactive to light.
Her facial movements are symmetrical, and there is no impairment of sensation on her face. Her motor strength is 5/5 in all four extremities. Her sensory examination is normal to light touch, pinprick, vibration, and position in all four extremities. Her reflexes are brisk in bilateral ankles, and they are otherwise normal. Her gait is normal, and she can do a tandem walk without difficulty.
The brain CT scan performed in the ED shows nonspecific gray matter changes bilaterally. The next morning a brain MRI scan reveals four small (approximately 1 cm each) enhancing gray matter lesions, with surrounding edema. Two lesions are in the left parietal lobe, one on the left frontal lobe, and one on the right frontal lobe.
An electroencephalogram (EEG) obtained after the patient’s left-sided weakness had resolved reveals a focal area of slowing in the right frontal region. The EEG is otherwise unremarkable.
Blood test results, including a complete blood cell count and electrolyte levels, are normal. Results of a lumbar puncture (LP) are normal, with no signs of infection, cancer, elevated white blood cells, or protein.
Course of illness
The patient is discharged from the hospital without a diagnosis. Levetiracetam (Keppra) is prescribed, but she does not remember to take it every day. She has another seizure 2 weeks after her first one. Her husband witnessed it at home, and it was very similar to her first one.
She has another brain MRI scan and a spine MRI scan. The brain MRI scan shows the same four lesions, but without the edema, and one of the lesions appears smaller. The spine MRI scan does not reveal any lesions.
She agrees to use her anticonvulsant as directed and has no further seizures. Two months later a brain MRI scan shows that all of her lesions are substantially smaller, to the point of being virtually unnoticeable if the image is not compared with the previous images. No new lesions are noted, and there is no edema near her four lesions.
She is tested for John Cunningham (JC) virus because her neurologist is concerned that her earlier course of corticosteroids predisposed her to infectious leukoencephalopathy caused by the virus. Her JC virus antibody antigen tests are both negative.
DIAGNOSIS: IDIOPATHIC LEUKOENCEPHALOPATHY
The patient received a diagnosis of idiopathic leukoencephalopathy. It was thought to be of an infectious etiology and presumed triggered by her course of corticosteroids. Her condition was considered atypical for several reasons. Her illness was milder than most cases of leukoencephalopathy. Infectious leukoencephalopathy is usually associated with severe immunosuppression (as seen with AIDS) or chemotherapeutic agents; it is rarely triggered by corticosteroids alone. It has been reported among patients treated for autoimmune conditions, such as ulcerative colitis and lupus.1
A diagnosis of leukoencephalopathy carries a poor prognosis, but reversible cases are often seen as well. Cases of posterior reversible leukoencephalopathy are more common than those involving the parietal and frontal regions, as occurred in this patient.
Conditions that must be ruled out include:
• Infectious or inflammatory encephalitis
• HIV infection
The lesions may be primary brain tumors or metastatic cancer. Some types of cancer can predispose to leukoencephalopathy by inducing immunosuppression. Infections could potentially be identified by LP or with a biopsy of the lesion.
A sudden vascular event that caused four strokes at once would require a cardiac and carotid evaluation to search for the source of an embolic shower. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is vascular condition that also should be considered. With CADASIL, there should be a family history, although some patients might not have an affected family member. And while infarcts in CADASIL typically involve white matter, gray matter involvement has been reported as well.2
• Unexplained brain lesions should be evaluated with repeated brain imaging
• When a patient has several brain lesions without a clear vascular etiology, imaging the spinal cord may be necessary as well
• Solid mass infections and isolated inflammatory lesions may not always produce cellular abnormalities detected by LP
1. Kikuchi S, Orii F, Maemoto A, Ashida T. Reversible posterior leukoencephalopathy syndrome associated with treatment for acute exacerbation of ulcerative colitis. Intern Med. 2016;55:473-477. doi: 10.2169/internalmedicine.55.5250.
2. Lambert C, Sam Narean J, Benjamin P, et al. Characterising the grey matter correlates of leukoaraiosis in cerebral small vessel disease. Neuroimage Clin. 2015;9:194-205. doi: 10.1016/j.nicl.2015.07.002.