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.
Glioblastoma is the worst form of primary brain tumour, and survival is already poor. Treatment is usually palliative with debulking surgery and radiotherapy. Dexamethasone, a corticosteroid, effectively reduces the swelling or oedema that the tumour evokes around it. Corticosteroids are therefore often the first treatment for glioblastoma because they almost immediately improve symptoms such as reduced consciousness, headache, and visual blurring.
It is, therefore, surprising when a study suggests that corticosteroids cause harm. But this is no ordinary study; it is a classic bench-to-bedside research which looked at patients with glioblastoma, and then devised a mouse model to study the real impact of steroids on the tumour.
The authors show that a ‘ dexamethasone-associated gene expression signature correlated with shorter survival’. They pass the verdict that corticosteroids are detrimental to survival and urge caution when prescribing dexamethasone.
Brain cancer is a horrible disease even among cancers. Apart from benign tumours such as meningioma, very few brain tumours have happy endings. It is however not all doom and gloom- there are many advances raising hope for the future of brain cancer. Here are 10 hope-raisers.
The challenge for every drug cancer treatment is to deliver the drug as close as possible to the tumour cells. This is particularly difficult for brain cancer because of the protective brain blood barrier (BBB). This shield is composed of the walls of the blood vessels, and the triple-layered sheath covering the brain called the dura.
What if the drugs could be sent across this barrier without breaching it? More Dr. Who than neuroscience, but this is what the ultrasonic screwdriver recently achieved to wide acclaim. Using ultrasound, the scientists successfully delivered chemotherapy drugs across the BBB. This press release from Sunnybrook Health Sciences Centre explains it further. The neurosurgeons used an MRI-guided focused low-intensity ultrasound to force drug microbubbles in the bloodstream across the blood-brain barrier. “The waves repeatedly compress and expand the microbubbles, causing them to vibrate and loosen tight junctions of the cells comprising the BBB. Once the barrier was opened, the chemotherapy flowed through and deposited into the targeted regions”. Very exciting SciFi stuff. Here is a simplified version from IFL Science titled Scientists Have Breached The Blood-Brain Barrier For The First Time And Treated A Brain Tumor Using An “Ultrasonic Screwdriver”.
8. Electromagnetic field therapy
Electromagnetic field therapy is a new area of brain tumour treatment and not conventional in any way. It however promises to improve survival of patients with glioblastoma who have received conventional radiotherapy and chemotherapy. I came across this in MNT under the title Use of type of electromagnetic field therapy improves survival for patients with brain tumor. This treatment is a form of tumor-treating fields (TTFields), “a treatment that selectively disrupts the division of cells by delivering low-intensity, intermediate-frequency alternating electric fields via transducer arrays applied to the shaved scalp”. The evidence for this is a trial reported in the Journal of the American Medical Association (JAMA) titled Alternating electric fields for the treatment of glioblastoma. It is not a panacea but any light at the end of the dreadful tunnel of brain cancer is worth exploring. It is a good sign that the FDA has approved this technology.
7. Pulsed electric field (PEF)
Another technique that is under investigation for treatment of brain cancer is pulsed electric field (PEF). This was the focus of a recent paper in Scientific Reports titled Targeted cellular ablation based on the morphology of malignant cells. PEFpreferentially targets and destroys malignant cells relatively sparing normal cells. The mechanism, if you are curious to know, is called high frequency irreversible electroporation (HFIRE). Or, in plain English, electric disruption of cells. This has reportedly been effective in dogs, and the challenge is to translate the benefits to humans.
Two recent papers have reported on cellular proteins which brain tumours depend on. These are therefore potential targets for future therapeutic interventions. The first is hypoxia inducible factor-1 (HIF-1) whichcancer cells produce when their oxygen supply is threatened. HIF-1 enables the cancer cells to produce new blood vessels (angiogenesis) thereby maintaining their supply of nourishing oxygen. This process is under investigation by researchers at Emory University.
The second property is related to proteins called sterol regulatory element-binding proteins (SREBPs). SREBP’s control the metabolism of glucose and fat in all cells, and researchers at Ohio State University are looking at ways to inhibit these proteins. This would potentially impair the ability of cancer cells to build their cell walls (membranes). Yes, only in mice again but still, hope. Here is a review of SREBP’s and cancer.
The news that Jimmy Carter has melanoma, and this had spread or metastasised to his brain, came as a shock to many of his admirers. It was therefore a relief when they learnt later that Carter’s cancer has all but cleared away. Very unusual to say the least, especially with a cancer as dreadful as melanoma. This remarkable achievement is attributable to an immunotherapy drug called Pembrolizumab, one of several types of drugs called humanised monoclonal antibodies.