I thought of how von Economo, the physician who had first identified the encephalitis lethargica, had spoken of postencephalitic patients as ‘extinct volcanoes.’ This seemed an apt comparison until L-DOPA came along, when I began to think of them as sleeping volcanoes, which might suddenly (sometimes dangerously) erupt with this new drug. But these patients were already manifestly ill – frozen, catatonic; whereas the lytico-bodig patients, seemingly, were perfectly well and active before their symptoms began. ‘But you can’t be sure of that on purely clinical grounds,’ said John. ‘You have no way of judging what may be going on at the cellular level.’ What had been going on, we wondered, in Euphrasia during those twenty-two years after she had left Guam?
Euphrasia was started on L-DOPA by her doctor in California in 1969 (this intrigued me, as it was the same year I had started my own post-encephalitic patients on L-DOPA). In ordinary Parkinson’s disease, the initial effects of the drug are smooth and steady and last for many hours, though sooner or later, its effects may become unstable, giving patients a brief period of fluidity, sometimes accompanied by chorea and other involuntary movements, followed in an hour or so by an intense immobility – a so-called on-off effect. Such on-off effects, I had found, tended to set in much earlier with my post-encephalitic patients – sometimes, indeed, from the very start, and Euphrasia too, John said, had shown reactions which were extreme and hyperbolic from the beginning. And yet despite its ups and downs, she continued to get a crucial benefit from L-DOPA, for it allowed her a few hours of relatively good function each day.
She had not had any medication for several hours when we stopped by, and she was in an ‘off’ state, sitting completely motionless in a chair, her head bent, almost jammed, on her chest, only her eyes still capable of any movement. There was extreme rigidity in all her limbs. Her voice was very soft, flat, almost inaudible, and devoid of any animation or expression. She drooled constantly.
John introduced us, and I took her hand and squeezed it gently She could not speak, but she smiled back, her eyes crinkling, and I could feel a faint squeeze in response.
With a conspiratorial wink to Euphrasia, I said to John, ‘I’ll show you something – or Euphrasia will.’ I managed, with some difficulty, to get her to her feet. Walking backward in front of her, holding her gnarled hands, cueing her all the time, I was able to guide her, with tiny, tottering steps, to the garden just outside. There was a rock garden in the form of a little hill, with irregular ledges and slopes. ‘Okay,’ I said to Euphrasia, pointing to a rock, ‘climb over this, you’re on your own – go!’ To John’s horror, and the nuns’, I took my hands off her, and let her go. But Euphrasia, who had been almost incapable of movement on the flat, featureless floor of the dayroom, lifted her leg high, and stepped boldly over the rock, and then over another one, and another, up to the top of the rock garden, without difficulty. She smiled, and climbed down again, as surefootedly as she had gone up. As soon as she reached the level ground, she was as helpless as before. John looked rather stunned at this, but Euphrasia still had a ghost of a smile on her lips – she was not in the least surprised at all. And had she been capable of speaking, she might have said, like so many of my post-encephalitic patients, ‘If only the world consisted of stairs!’
It was two o’clock, the nun said, time for her medicine. She brought Euphrasia, now sitting in the dayroom once again, a tiny white pill with some water. Fourteen minutes after receiving her L-DOPA – we timed this, as if waiting for a chemical reaction, or explosion – she suddenly jumped to her feet with such energy her chair fell over backward, hurtled along the corridor, and burst into lively, even rambunctious, conversation, bursting with all the things she had wanted to say, but could not while she was frozen. This was not just a disappearance of her parkinsonism, her motor problems, but a transformation of her senses, her feelings, her whole demeanor. I had not seen anything like this in more than twenty years, and was both stunned (though I had half expected her to show such a reaction) and a bit nostalgic – Euphrasia especially reminded me of my postencephalitic patient Hester, in whom there was a similar, instantaneous transformation, with no intermediary state, no warming-up period whatever.
But it was not a wholly simple ‘awakening’ for Euphrasia, any more than it had been for hyperbolic Hester. For along with the motor animation, the liveliness, the playfulness, which suddenly came on her, there came a tendency to wisecrack, to tic, to sudden lookings and touchings, to tossing and darting, to jabbing and lunging – a dozen strange impulsions, a drivenness of body and mind. There was this tremendous rush of life, of extravagant activation, both healthy and pathological, and then, twenty minutes later, a re-descent into her original state, coupled with repeated yawning, a sudden complete lethargy.
‘What do you think of that, eh?’ asked John, at my side, eagerly. ‘Remind you of anything?’
When he is not seeing patients, John teaches at the Guam Memorial Hospital in Tamuning and does research in his laboratory there. He has lobbied hard for more research funding to be put into local facilities, and would like to establish a complete center on the island for investigating the lytico-bodig, with sophisticated neuropathology equipment and facilities for MRI scans and other brain imaging. At present, many of these studies have to be done on the mainland, while much of the epidemiological work – interviewing patients and piecing together extensive family trees – as well as basic clinical and lab work of various kinds, is done here on the island.
He showed me into his lab; he had something special he wanted me to see. ‘Let me show you these slides, Oliver,’ said John, waving me over to a microscope. I looked through the eyepiece, under low power first, and saw pigmented cells, symmetrically arranged in a V.
‘Substantia nigra,’ I said. ‘Many of the cells are pale and depigmented. There’s a lot of glial reaction, and bits of loose pigment.’ I shifted to a higher power, and saw a huge number of neurofibrillary tangles, densely staining, convoluted masses, harshly evident within the destroyed nerve cells. ‘Do you have samples of cortex, hypothalamus, spinal cord?’ John handed these to me, I looked at them one after another – all were full of neurofibrillary tangles.
‘So this is what lytico-bodig looks like,’ I said, ‘neurofibrillary degeneration everywhere!’
‘Yes,’ said John, ‘that’s very typical. Here’s another case – have a look at this.’ I went over it as before; the findings were very similar, and there was much the same distribution of tangles.
‘All the lytico-bodig cases look like this?’ I asked.
‘Actually, Oliver’ – John smiled broadly – ’what you’re looking at now isn’t lytico-bodig at all. It’s your disease, it’s postencephalitic parkinsonism – these slides were sent to me by Sue Daniel in London.’
‘I haven’t done much pathology since I was a resident,’ I said, ‘and I’m no expert – but I can’t tell them apart.’
John grinned, pleased. ‘Here, I have some more slides for you.’ I looked at this new series, starting with the substantia nigra, the midbrain, moving up and down from there.
‘I give up,’ I said, ‘I can’t tell whether it’s lytico-bodig or post-encephalitic parkinsonism.’
‘Neither,’ said John. ‘This is my disease, progressive supranuclear palsy. In fact, it’s from one of the original cases we described in 1963 – even then we wondered about its similarity to post-encephalitic parkinsonism. And now we look at the Guam disease…and all three look virtually the same.