A 48-year-old chemistry professor was admitted to Dartmouth–Hitchcock Medical Center, in Lebanon, New Hampshire, on January 20, 1997, with a five-day history of progressive deterioration in balance, gait, and speech. She had lost 6.8 kg (15 lb) over a period of two months and had experienced several brief episodes of nausea, diarrhea, and abdominal discomfort.

The patient recalled that in August 1996, while transferring liquid dimethylmercury from a container to a capillary tube, she spilled several drops from the tip of the pipette onto the dorsum of her gloved hand. (A subsequent review of her dated laboratory notebooks, a history provided by a coworker, and examination of the dated materials used in the experiment later pinpointed the date as August 14, 1996.) She reported that she had cleaned up the spill and then removed her protective gloves.

The patient was thin but appeared healthy and was appropriately concerned about her neurologic problems. The examination showed moderate upper-extremity dysmetria, dystaxic handwriting, a widely based gait, and mild “scanning speech.” The results of routine laboratory tests were normal. The results of computed tomography (CT) and magnetic resonance imaging (MRI) of the head were normal except for the incidental finding of a probable meningioma, 1 cm in diameter. The cerebrospinal fluid was clear, with a protein concentration of 42 mg per deciliter and no cells.

Because of the possibility of methylmercury neurotoxicity, blood and urine samples were sent for urgent measurement of mercury content. In view of the long interval between the date of exposure to mercury and the onset of neurologic symptoms (154 days) as well as the rapid progression of symptoms, other causes of acute cerebellar dysfunction were considered.

In the ensuing days, the patient noted tingling in her fingers, brief flashes of light in both eyes, a soft background noise in both ears, and progressive difficulty with speech, walking, hearing, and vision (constricted visual fields). A preliminary laboratory report indicated that the whole-blood mercury concentration was more than 1000 μg per liter. Chelation therapy with oral succimer (10 mg per kilogram orally every eight hours) was begun on day 168 after exposure. The next day, the following laboratory values were reported: whole-blood mercury, 4000 μg per liter (normal range, 1 to 8; toxic level, >200); urinary mercury, 234 μg per liter (normal range, 1 to 5; toxic level, >50).13,14

The patient's neurologic deterioration continued; neuropsychiatric testing revealed marked deficits in all areas. Chelation therapy was initially successful, with an increase in urinary excretion of mercury from 257 μg per 24 hours (before chelation therapy) to 39,800 μg per 24 hours. Vitamin E was added to the regimen as a potentially protective antioxidant.

The patient was transferred to Massachusetts General Hospital in Boston. Vitamin E and succimer were continued. An exchange transfusion reduced the mean whole-blood mercury concentration from 2230 μg per liter before the procedure to 1630 μg per liter 2 hours afterward, but reequilibration resulted in a concentration of 2070 μg per liter 16 hours later. The mercury content of bile was 30 to 99 μg per liter. Repeated CT and MRI scans of the head remained normal, with no evidence of occipital or cerebellar damage. Audiometry revealed mild-to-moderate sensorineural hearing loss. Neuro-ophthalmologic testing revealed moderately constricted concentric fields, with no evidence of papilledema. On February 6, 22 days after the first neurologic symptoms developed (and 176 days after exposure), the patient became unresponsive to all visual, verbal, and light-touch stimuli.

Figure 1. Figure 1. Blood Concentrations and Urinary Excretion of Mercury over Time in a 48-Year-Old Woman. The values are plotted on a logarithmic scale. The elimination half-lives of mercury were 29 days in plasma, 33 days in whole blood, and 37 days in red cells.

Figure 2. Figure 2. Mercury Content of a Sample of Hair. The sample was obtained on January 31, 1997 (day 170 after exposure). The mercury content of a single strand of hair was measured every 2 mm from the scalp end. The apparent rate of hair growth was 78 mm over a period of 170 days, or 1.38 cm per month. On the basis of this rate, there was a lag phase of 17.4 days, followed by the distribution of mercury from blood to hair during a period of 21.8 days (half-life, 5.6 days) and a subsequent decline in the mercury content of hair (and presumably blood) during a period of 130.7 days (half-life, 74.6 days). These two first-order processes are represented by the curve, with the circles indicating the observed data.

The patient was transferred back to Dartmouth–Hitchcock Medical Center, and aggressive general support was continued, along with 21-day cycles of chelation therapy with succimer (10 mg per kilogram given orally every 12 hours). The decline in blood mercury concentrations over time is shown in Figure 1. Mercury half-lives (with chelation therapy) were 29 to 37 days. Urinary excretion of mercury declined rapidly despite ongoing chelation therapy (Figure 1). Analysis of a long strand of hair revealed that after a brief lag, the mercury content rose rapidly to almost 1100 ng per milligram (normal level, <0.26 ng per milligram; potentially toxic level, >50 ng per milligram)15 and then declined slowly, with a half-life of 74.6 days (Figure 2).

The patient's neurologic status was marked by periods of spontaneous eye opening, but without awareness of or any response to visual, sound, or light-touch stimuli. The Babinski sign was equivocal, and decerebrate and decorticate posturing were absent. Painful stimuli resulted in limb withdrawal. Corneal and pupillary reflexes were sluggish but present. Spontaneous yawning, moaning, and limb movements occurred, with periods of agitation and crying, requiring large doses of chlorpromazine and lorazepam. Her condition appeared to resemble a persistent vegetative state with spontaneous episodes of agitation and crying.

Testing of family members, laboratory coworkers, and laboratory surfaces failed to reveal any unsuspected mercury spills or other cases of toxic blood or urinary mercury concentrations.

We could find only three previously reported cases of poisoning with dimethylmercury, all of which were fatal.3,16 Equally bleak outcomes have been reported in patients with severe methylmercury toxicity.2 In view of the dismal prognosis and after more than three months of aggressive treatment and support, the patient's advance directives were followed, and she died peacefully on June 8, 1997, 298 days after exposure.

Figure 3. Figure 3. Cerebellar Hemispheric Sections from the Patient (Left) and from a Woman of Approximately the Same Age without Neurologic Disease (Right). Widespread shrinkage of the folia and diminution of the cerebellar cortical thickness are evident in the section from the patient.

At autopsy, dehydration and bronchopneumonia were noted. The cortex of the cerebral hemispheres was diffusely thinned, to 3 mm. The visual cortex around the calcarine fissure was grossly gliotic, as was the superior surface of the superior temporal gyri. The cerebellum showed diffuse atrophy of both vermal and hemispheric folia (Figure 3). Microscopical study showed extensive neuronal loss and gliosis bilaterally within the primary visual and auditory cortices, with milder loss of neurons and gliosis in the motor and sensory cortices. There was widespread loss of cerebellar granular-cell neurons, Purkinje cells, and basket-cell neurons, with evidence of loss of parallel fibers in the molecular layer. Bergmann gliosis was well developed and widespread.

An extremely high mercury content was found in the frontal lobe and visual cortex (average value, 3.1 μg per gram, or 3100 ppb), liver (20.1 μg per gram), and kidney cortex (34.8 μg per gram). The mercury content of the brain was approximately six times that of whole blood at the time of death and was much higher than levels in brain samples obtained at autopsy from patients not previously exposed to mercury (2 to 50 ppb).17