Imaging is central to neurological practice. It doesn’t take much to tempt a neurologist to ‘order’ or ‘request’ an MRI or a CT. In appropriate circumstances the imaging is a DAT scan, and with a bit more savvy, exciting imaging modalities such as amyloid scans and tau PET scans. In the playpen of the neurologist, the more ‘high tech’ the imaging technology, the more cutting-edge it feels-even if it doesn’t make much of a difference to the patient. Ultrasound on the other hand is the mongrel of imaging technologies. Too simple, too cheap, too available, too unsophisticated-not better than good old X-rays. It is safe to assume that the pen of the neurologist hardly ever ticks the ultrasound box. What for?
And yet, ultrasound has an established, even if poorly appreciated, place in neurological imaging. It is perhaps best known for its usefulness in assessing carpal tunnel syndrome at the wrist. But, for the neurologist, CTS is sorted out by wrist splints, steroid injections, and decompression surgery-forgetting that there may just be a ganglion, a cyst, or a lipoma lurking in there. Ultrasound also has a place in the assessment of muscle disorders, picking up anomalies and detecting distinctive muscle disease patterns. The only problem is that, even when radiologists and neurologists put their heads together, they struggle to understand what the patterns actually mean. And since the first pass of this blog post, I was reminded of the place of ultrasound-guided lumbar puncture in improving the safety and accuracy of this otherwise blind procedure. And there are even guidelines to help takers. My guess is that most neurologists prefer the thrill of hit-and-miss that goes with conventional LP. For many reasons therefore, the ultrasound box remains un-ticked.
Despite these limitations, the place of ultrasound remains entrenched in neurological practice. Indeed, ultrasound has been spreading its wings to exotic places, broadening its range, and asserting its presence. Perhaps it is time to reconsider the humble ultrasound, and to catch up with what it has been up to. Here then are 3 emerging roles of ultrasound in neurology
The blood brain barrier is a rigidly selective barricade against most things that venture to approach the brain-even if their intentions are noble. This is a huge impediment to getting drugs to reach the brain where they are badly needed. It is therefore humbling that it is the simple ultrasound that is promising to smuggle benevolent drugs across the blockade to aid afflicted brains. This was reported in the journal Science Translational Medicine, and the article is titled Clinical trial of blood-brain barrier disruption by pulsed ultrasound. The trial subjects were people with the notorious brain tumour, glioblastoma. They were injected with their conventional chemotherapy drugs, delivered along with microbubbles. The blood brain barrier was then repeatedly ‘pelted’ with pulsed ultrasound waves; this seem to leapfrog the drugs into the brain in greater than usual concentrations, enough to do a much better job. This surely makes films such as Fantastic Voyage and Inner Space not far-off pipe-dreams.
Neurofibromatosis (NF) is one of the major neurocutaneous disorders neurologists see. These are disorders which primarily affect the nervous system and have prominent skin manifestations. Also known as phakomatoses, they are typified by abnormal growths and a variety of cancers. They include well-defined conditions such as tuberous sclerosis complex (TSC), Sturge-Weber syndrome (SWS), von Hipple Lindau disease (VHL), schwannomatosis, and the various PTEN hamartoma tumour syndromes. There are two types of neurofibromatosis, NF1 and NF2. NF2 is characterised by vestibular schwannomas, tumours arising from the sheath that encases the nerve that control balance, and by meningiomas, tumours of the covering of the brain.
NF1, also known as von Recklinghausen disease is, by far, the commoner form of neurofibromatosis. It is readily recognised on the skin by the frequently multiple and disfiguring nerve tumours called neurofibromas. Other benign skin lesions include the coffee-coloured skin lesions aptly called cafe-au-lait spots, armpit lesions called axillary freckles, and small lesions on the iris of the eyes called Lisch nodules. More sinister skin lesions called malignant peripheral nerve sheath tumours (MPNST) are, as the name implies, capable of spreading to other organs such as the lungs. Other sinister tumours in NF1 include gliomas of the brain and optic nerve, gastrointestinal stromal tumours (GIST) of the gut, and rhabdomyosarcomas of bone.
What can neurologists do for people with neurofibromatosis? Traditionally, nothing much apart from watchful waiting. We would monitor for the development of tumours by regular surveillance MRI scans of the brain and spine, and refer people with painful, compressive, or malignant lesions to the plastic surgeons or neurosurgeons to do what they do best, taking things out. Surgery may work fine for simple neurofibromas, but it is less practical for the complex or plexiform type. Thankfully, many neuroscientists are working hard, looking at different approaches to managing neurofibromas. To illustrate, below are 5 emerging treatments for neurofibromatosis.
In a 2016 paper in the New England Journal of Medicine,Eva Dombi and colleagues investigated the effect of selumetinib, an oral inhibitor of an enzyme called MAPK kinase (MEK) in 24 children with NF1. The paper, titled Activity of selumetinib in neurofibromatosis type 1-related plexiform neurofibromas, showed that selumetinib reduced the size of neurofibromas, and there was evidence that it improved pain and reduced disfigurement.
Brian Weiss and colleagues investigated the effect of sirolimus, an inhibitor of mTOR complex 1, in 46 people with NF1 and published their findings in the journal Neuro-Onclology. The paper, titled Sirolimus for progressive neurofibromatosis type 1-associated plexiform neurofibromas, demonstrated that sirolimus prolonged the time to progression (TTP) of plexiform neurofibromas by about 4 months. A modest effect they admit, but nevertheless, a hope-raising effect.