Category Archives: neurology

Ultrasound enhanced tPA for stroke

An article in yesterday’s NEJM on Ultrasound-enhanced systemic thrombolysis for acute ischemic stroke was the first I had seen on thrombolysis for CVA in quite a while (the last major trial on t-PA for stroke published in the NEJM, which I reviewed here, was 9 years ago). And a quick PubMed search yielded this study from Cleveland, which indicates that only about 2% of strokes nationwide receive t-PA, mainly because of the 3 hour time requirement from onset of symptoms.

Ultrasound energy has been shown to facilitate the activity of fibrinolytic agents. Experimental work with lower frequency (Kilohertz) ultrasound in conjunction with t-PA had previously shown an increased risk of hemorrhage. This effect has not been noted with higher frequency (MHz) transcranial diagnostic ultrasound which has been used to look at the patency of cerebral arteries. The current phase II trial was designed to examine the effects of continuous, high frequency transcranial doppler monitoring, in conjunction with t-PA, on hemorrhage, patency and recovery rates.

126 stroke patients who presented early with evidence of abnormal flow through the middle cerebral artery were randomized into two groups of 63 patients. Both groups received t-PA, and both groups had transcranial doppler measurements that checked the flow at 0, 30, 60, 90 and 120 minutes. Patients in the target, ultrasound group had diagnostic ultrasound insonation that was continuous for the two hours; patients in the placebo group only received the diagnostic ultrasound at the prespecified times.

Patients in the target ultrasound group did better, in terms of both recanalization and clinical improvement (NS, however), without any difference in intracranial hemorrhage:

Continuous ultrasound Placebo ultrasound
Complete recanalization within 2 hours 46% 18% (p<0.001)
Clinical recovery within 2 hours 29% 21% (NS)
Favorable outcome at 3 months (modified Rankin score of 0 or 1) 42% 29% (NS)

These results are encouraging and presumably more studies will be undertaken to see what the optimal ultrasound approach should be (energy level, duration of therapy). If this pans out, the benefit of thrombolytic therapy would be more convincing than it is at present, and might bolster enthusiasm for its use. The addition of another technological requirement to stroke management would complicate matters somewhat, and might make a more effective case for centralizing stroke treatment.

Most fascinating is a report, cited by Medpundit, that indicates a possible beneficial effect of ultrasound alone in the management of stroke! This comes from an anecdotal report by a physician in Scotland.

Vestibular rehabilitation for dizziness

In the October 19 issue of Annals of Internal Medicine is a study from the UK of the effectiveness of primary care-based vestibular rehabilitation for chronic dizziness. Primary care patients with a history of labyrinthine dizziness that had lasted at least two months were randomized in a single blind fashion to receive nurse-taught vestibular rehabilitation exercises or usual care; after three months the patients who had received the usual care were crossed-over to vestibular rehabilitation.

The rehabilitation exercises consisted of increasingly aggressive maneuvers designed to stress the vestibular system and provoke dizziness (such as turning the head with eyes open, then closed). These exercises were to be done once or twice daily. The details of the vestibular rehabilitation, and a detailed patient handout explaining the exercises, are available at the Annals website. Patients were evaluated using various questionnaires and forms, and with a device that measured postural stability.

The results indicated that patients did indeed improve more with the vestibular rehabilitation than without.

I found the results of this study to be frustrating. There are two things that I would have liked to find out: what percentage of patients in each group felt, say, “cured or almost completely cured” or “very substantially better” and whether or not there was any difference in the number of falls in either group. The authors bombard us with data, but do not answer these simple questions directly.

I am happy to hear that the Vertigo Symptom Scale was 13.3 in the usual care group and only 9.88 in the rehabilitation group. I am delighted that the Dizziness Handicap Inventory went from 35.88 to 31.09. I am impressed that the Short Form-36 (physical functioning) was 25.95 vs. 27.14. But what does all this mean? The authors do state that 67% of the treated group reported clinically significant improvement, compared with 38% of the usual care group, but what exactly constitutes clinically significant improvement? Did any of these patients actually fall, before or during the study? Nothing about this issue.

Since so many of my older patients complain of unsteadiness on their feet, I would love to recommend exercises to help them. Most likely, vestibular rehabilitation would be helpful and effective. But it would be nice to have some simpler, more comprehensible data about it. I understand that tables full of statistically significant numbers are necessary to get published, but it should be possible to sneak in a patient’s actual assessment of treatment efficacy somewhere.