by Cesare Peccarisi
For the delicate operation, focused ultrasonography, which has so far only been tested on adults, was used. The little ones, affected by a serious form of pneumonia, are doing well
The neurosurgeons of the Besta Neurological Institute in Milan, the first in the world, used MRgFUS (Magnetic Resonance guided Focused UltraSound) on children, having to resolve a situation that seemed to have no way out: treat two dystonic children (which causes serious movement disorders) by inhibiting the altered activity of their globi pallidi on both sides of the brain without being able to use DBS (deep brain stimulation) because they had been infected with a form of pneumonia that prevented exposure of the intracranial space.
The story of the two little patients
The two young patients who turned to Besta came from Sardinia where iron pollution is very high due to the numerous extractive mines in the region and in fact they suffered from a rare NBIA type dystonia (Neurodegeneration with Brain Iron Accumulation, i.e. neurodegeneration by accumulation cerebral iron), a mineral that ends up mainly in the globi pallidi, causing an inexorably progressive form including developmental delay and cognitive decline for which there was no cure. The first, 7 years old and already under treatment at Besta for two years, was successfully operated on in September 2023.
Bypass the blood brain barrier
As Galileo Galilei said: «Behind every problem there is an opportunity» and this time it was seized by the Besta neurosurgeons, directed by Francesco DiMeco, who decided to use FUS in a minor for the first time in the world, managing to solve the problem of the altered function of the pallidum without damaging the blood-brain barrier, but burning them from the outside using focused ultrasound. In fact, the brain is always protected by the blood-brain barrier that covers it like an impenetrable sheath because it lacks the immune defenses that the rest of the body has, so much so that if a bacterium or a virus manages to overcome it we know full well what trouble it is in for. I meet those affected by encephalitis.
Generally, that is, in the absence of systemic infections, treating malfunctioning brain areas via DBS is now a routine practice not only at Besta, but in all similar institutions around the world. This occurs both in adults and in children in whom it is only less frequent, as are dystonias in this age group.
The different forms of dystonia
The dystonia caused in the two little ones by the accumulation of iron is a movement disorder that actually occurs for many causes and in multiple forms, but all are characterized by large and slow repetitive movements, anomalous and tortuous postures or uncontrollable muscle tremors. Dystonias can affect the muscles of the face or neck, or those of the limbs, with sudden twisting movements and abnormal postures of the trunk. Some take picturesque definitions ranging from spasmodic torticollis to scribe’s or musician’s cramp, but the worst forms such as laryngeal dysphonia and spasmodic dysphonia which prevent speaking or eating and drinking cause a serious decline in the quality of life.
Nor should we forget the so-called blepharospasm which compromises vision due to the involuntary, brief or sustained closure of the palpebral fissure due to bilateral, synchronous and stereotyped spasms of the orbicularis muscles of the eyelids.
Severe forms
In rare cases these patients undergo serious deterioration, evolving into the so-called status dystonicus which requires assistance in intensive care due to metabolic complications and adequate sedation and ventilation. The Besta Institute has recently dedicated an entire new wing of the hospital equipped with latest generation technologies such as thermometry, neuronavigation, magnetic resonance imaging from 1.5 to 7 tesla, which are opening also the path to the treatment of brain tumors in a completely new way that promises to revolutionize oncological neurosurgery.
The new frontiers: neuro-oncology
«Although we are taking the first steps, FUS could be used in an ever-increasing number of neurological diseases with applications ranging from oncology to cerebrovascular disorders, to neuro-functional ones and even to neuro-immune modulation – declares Professor Francesco DiMeco, who directs the team of neurosurgeons at Besta and also has a position at the Department of Oncological Neurosurgery at the Johns Hopkins Medical School in Baltimore -. To evaluate the effects of FUS in a non-invasive and precise way, today, in addition to the latest generation magnetic resonance imaging, we have cutting-edge equipment including acoustic windows with which to verify the effects of the ultrasonic beams sent millimeter by millimeter.”
Microvarchi
«The application of FUS in the oncology field is based on the possibility of opening transient micro-gaps in the blood-brain barrier, just long enough for chemotherapy drugs to cross it and obtain those effects that until now we couldn’t have because the barrier blocked them as it does with viruses. In North America they have already been doing this for some time for primary or secondary glioblastomas and will soon do so for brain metastases. We were the first to do it in Europe. To date, there have been 23 cases treated with barrier perforation and the results show that the method works and there are no unwanted side effects”, continues DiMeco.
Tumor markers
Given the good results, we have already started a study to see if, once the barrier has been pierced, it is possible to detect brain tumor markers in the blood that previously could not escape and thus gain precious time for treatment. Another study that has already started concerns the treatment of brain metastases from lung adenocarcinoma, a common occurrence often burdened by late diagnosis due to their initial asymptomatic nature. Being able to act earlier and more directly without blocking the blood-brain barrier would allow us to make up for often lost time”, concludes the expert.
The previous record with DBS
After 24 years, the Besta Neurological Institute of Milan is the protagonist of another world record: on 14 July 2000, its doctors carried out the first treatment in the world with DBS of chronic drug-resistant cluster headache, the so-called suicide headache which in one unfortunate patient he no longer responded to any treatment, transforming his life into hell. The technique was copied all over the world and also used successfully in other neurological diseases such as Parkinson’s or dystonias which, after Parkinson’s and essential tremor, are the most frequent movement disorder from which 40 thousand Italians suffer.
Invasive technique
DBS is an invasive technique which, a bit like Elon Musk’s recent Neuralink, requires the intracranial positioning of a mini-stimulator which uses filaments as thin as hair to send microimpulses into different brain areas depending on the pathology to be treated and which requires a rechargeable battery to be inserted into the chest. In these twenty years, many softer techniques have been developed to avoid ending up under the knife of the neurosurgeon, always acting from the outside via electrical microimpulses which, however, have not demonstrated the same precision.
The “heir”
The only non-invasive technique that can be considered the worthy heir of DBS is FUS. As reported last year in the prestigious New England Journal of Medicine by Besta doctors in a study conducted with Canadian and European colleagues, the technique abolishes the tremor of Parkinson’s disease without requiring any neurosurgical intervention because it acts from the outside and not through microimpulses electrical as DBS does, but with focused ultrasound that generates heat, burning the brain area responsible for the disorder which is centered with ultra-millimetre precision by magnetic resonance imaging. The treatment lasts a few seconds and requires a single 2-hour session mostly due to the preparation of the patient who always remains awake to leave the operating room with minimal help from the operators.
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February 17, 2024 (modified February 17, 2024 | 2.32 pm)
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