neurocirugia

#Conheça as bases do tratamento cirúrgico da Doença de Parkinson

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parkinson

Conheça as bases do tratamento cirúrgico da Doença de Parkinson

O tratamento cirúrgico para os distúrbios motores da doença de Parkinson é pregresso às medicações hoje existentes, no entanto, eram baseadas em abordagens do sistema nervoso periférico (com rizotomias e simpatectomias) e abordagem ao sistema nervoso central (com corticectomias e secções do pedúnculo cerebral).

Atualmente, além das diversas terapias medicamentosas existentes, as cirurgias se tornaram muito mais precisas e menos lesivas, sendo em quase totalidade realizada por estereotaxia. A abordagem aos distúrbios do movimento se aplica desde a abordagem as distonias ao tratamento da síndrome parkinsoniana (rigidez, bradicinesia, tremor e instabilidade postural por perda dos reflexos posturais) cujo o principal protótipo é a Doença de Parkinson (DP).

Após 1968, com a criação da levodopa, o tratamento cirúrgico passou a ser reservado como adjuvante ao tratamento com fármaco no intuito de controlar os distúrbios motores gerados pelo uso crônico.

Critérios de indicação da doença de Parkinson

Alguns critérios como idade mínima e máxima, estadiamento e tempo mínimo de doença ainda são controversos, mas a maioria dos serviços assume como critérios os seguintes:

  1. Certeza diagnóstica da doença de Parkinson, preferencialmente com diagnóstico feito por um neurologista com experiencia em distúrbios do movimento.
  2. Resposta inquestionável à levodopa (em pacientes que possuem história compatível de doença de Parkinson), de sintomas assimétricos.
  3. Melhora nos escores motores com o teste de sobrecarga de levodopa.
  4. Grau igual ou menor a 4 na escala de Hoehn e Yahr
  5. Identificar os sintomas motores que podem ser melhorados cirurgicamente.
  6. Identificar os sintomas que mais limitam o paciente.
  7. Investigação e exclusão de lesões prévias no exame de imagem.
  8. Identificar, e caso existam distúrbios psiquiátricos, se esses irão permitir a cooperação para realizar a cirurgia.
  9. Avaliação da função cognitiva com estudos neuropsicológicos.
  10. Ajustar as expectativas e discutir os reais benefícios da cirurgia.

A escolha do alvo terapêutico

Primeiramente, deve se ter em mente que a escolha do alvo deve ser individualizada para cada paciente de acordo com os sintomas predominantes. Porém, os alvos com maiores evidências de resultados são o Globo Pálido Interno (GPI) e o Núcleo Subtalâmico (NST). O grande beneficio do GPI se dá em pacientes que predominam as discinesias e já possuem algum grau de déficit cognitivo, pois ao utilizar o NST poderia piorar a fluência verbal.

A escolha do NST é bem utilizada quando se objetiva a melhora dos sintomas cardinais e agrega o beneficio de gerar maior vida útil da bateria, pois os parâmetros utilizados são menores comparativamente ao GPi, além de diminuir consideravelmente as doses de levodopa, a qual deve ser diminuída lentamente com risco de indução de depressão com ideação suicida se retirada rapidamente.

O núcleo pedunculopontino (NPP) tem como característica a melhora dos sintomas axiais como a marcha, tendo como possibilidade ser estimulado junto ao NST pra que possa haver melhora tanto nos sintomas axiais e apendiculares respectivamente. No entanto, ainda é considerado por muitos centros como experimental. O Núcleo Ventral Intermediário (VIM) do tálamo foi tido como principal alvo nos casos em que há predomínio de tremor e este se faz de forma incapacitante, porém não há melhora na rigidez.

Hoje sua indicação é restrita a pacientes com DP unilateral, com evolução lenta e tremor intratável. Em pacientes que possuem como principais sintomas o tremor, mas apresentem outros sintomas exuberantes como bradicinesia e rigidez, o NST é o melhor alvo a ser escolhido. Apesar de poder ser utilizada a técnica bilateral, tanto por estimulação cerebral profunda quanto por lesão bilateralmente, ambas as técnicas podem evoluir com alteração de fala e distúrbios cerebelares quando realizado nos dois hemisférios.

Métodos ablativos ou neuromodulação qual escolher?

Não se pode dizer que um método novo é melhor que o anterior, só pelo fato dele ser o com maior tecnologia ou pelo simples fato de ser mais novo. Como tudo na vida, ambos os métodos possuem suas características quando a qualidades e defeitos, e devem ser usados de acordo com a individualizado de cada caso.

Os procedimentos ablativos têm como característica o baixo preço, simplicidade e maior acessibilidade, principalmente em países em desenvolvimento, onde o recurso financeiro no sistema público de saúde é escasso. Os resultados equivalem ao método de estimulação cerebral profunda, cuja desvantagem é a impossibilidade de reverter possíveis déficits causados pela lesão, e a impossibilidade de ser realizado lesão bilateral.

A neuromodulação tem como ponto positivo a possibilidade regular a intensidade e a extensão da área alvo, além de poder ser implantado bilateralmente. Assim como todo sistema eletrônico, o gerador do DBS possui uma vida útil como qualquer marcapasso, necessitando submeter o paciente a uma nova cirurgia a cada troca, além do alto custo ser incomparavelmente maior. Vale ressaltar que, ao se decidir implantar um sistema de DBS, o paciente tem que estar consciente que sempre deverá estar próximo a um centro médico para os devidos ajustes do aparelho.

Como é o procedimento cirúrgico?

A medicação do paciente é suspensa 12h antes da realização da cirurgia. Então é fixado um halo de estereotaxia no paciente sob anestesia local, em que a base deste deve estar localizada no plano orbitomeatal, que na maioria das vezes é paralela à linha intercomissural que liga a comissura anterior (AC) à comissura posterior (PC) e tem com seu ponto médio, o Ponto Médio Comissural (PMC).

Os parafusos devem ser colocados 3 cm acima do rebordo orbitário para evitar artefatos na linha AC-PC. É então realizada uma tomografia computadorizada ou ressonância se o sistema for compatível, com aquisição volumétrica com cortes de 1 mm, para que a imagem possa ser processada e utilizada como plano cartesiano para identificação dos núcleos cerebrais após cruzamento dos dados com auxilio de um software, que combina a tomografia com o halo e uma ressonância prévia nas sequencias ponderadas em T1 com contraste (avaliação dos vasos), T2 e Inversion recever (visualização anatômica nos núcleos).

Localização do Alvo

O alvo estereotáxico pode ser identificado de duas maneiras, de forma direta – olhando anatomicamente o local a ser lesado, ou de forma indireta, ao se calcular as coordenadas anatômicas. O lado a ser operado é o contralateral aos piores sintomas.

Intercomissural

NST: 11-13 mm lateral, 3-4 mm posterior e 4-5 mm inferior ao PMC.
Gpi: 19-21 mm lateral, 2-3 mm anterior e 4-6 mm inferior ao PMC.
VIM:10-12 mm lateral à parede do III ventrículo, no mesmo nível da linha intercomissural e 6 mm anterior à CP.

Os planos cartesianos são baseados em 3 eixos: X (médiolateral), Y (anteroposterior) e Z (superoinferior).

A cirurgia

A cirurgia propriamente dita consiste na introdução do eletrodo para ablação ou estimulação através de um orifício de trepanação, baseados nos parâmetros previamente citados e refinado a localização com a utilização de microrregistro, que capta a despolarização celular dos neurônios, podendo assim auxiliar na confirmação da localização-alvo.

Além da confirmação com o microrregistro, o paciente tem que estar acordado e cooperativo para que execute as funções e movimentos solicitados para que se possa identificar possíveis complicações, como inadequado posicionamento, cursando com acometimento da capsula interna, se exteriorizando com hemiplegia contralateral.

Complicações

A complicação mais frequente é o sangramento cerebral profundo, que geralmente é pequeno e assintomático. Esta complicação apresenta uma incidência de 1% dos casos. Outra complicação, porém mais associada ao implante de DBS, é o risco de infecção, que varia de 1,5 a 22%, sendo necessária na maioria das vezes a retirada do sistema acometido. Em pacientes submetidos a implante de eletrodo possuem uma incidência de 4-5% de complicações com o sistema, como migração ou quebra do cabo.

 

PebMed

Autor:

Referências:

  • SHUKLA, Aparna Wagle & OKUN, Michael Scott. Surgical Treatment of Parkinson’s Disease: Patients, Targets, Devices, and Approaches. Neurotherapeutics, dezembro de 2013. DOI 10.1007/s13311-013-0235-0

#The Brain That Remade Itself

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Doctors removed one-sixth of this child’s brain — and what was left did something incredible

Credit: iLexx/Getty Images

Iput my hand on a bishop and slide it several squares before moving it back. “Should I move a different piece instead?” I wonder to myself.

“You have to move that piece if you’ve touched it,” my opponent says, flashing a wry grin.

Fine. I move the bishop. It’s becoming increasingly obvious to me now — I’m going to lose a game of chess to a 12-year-old.

My opponent is Tanner Collins, a seventh-grade student growing up in a Pittsburgh suburb. Besides playing chess, Collins likes building with Legos. One such set, a replica of Hogwarts Castle from the Harry Potter books, is displayed on a hutch in the dining room of his parents’ house. He points out to me a critical flaw in the design: The back of the castle isn’t closed off. “If you turn it around,” he says, “the whole side is open. That’s dumb.”

Tanner Collins, Credit: Courtesy of Nicole Collins

Though Collins is not dissimilar from many kids his age, there is something that makes him unlike most 12-year-olds in the United States, if not the world: He’s missing one-sixth of his brain.

Collins was three months shy of seven years old when surgeons sliced open his skull and removed a third of his brain’s right hemisphere. For two years prior, a benign tumor had been growing in the back of his brain, eventually reaching the size of a golf ball. The tumor caused a series of disruptive seizures that gave him migraines and kept him from school. Medications did little to treat the problem and made Collins drowsy. By the day of his surgery, Collins was experiencing daily seizures that were growing in severity. He would collapse and be incontinent and sometimes vomit, he says.

When neurologists told Collins’ parents, Nicole and Carl, that they could excise the seizure-inducing areas of their son’s brain, the couple agreed. “His neurologist wasn’t able to control his seizures no matter what medication she put him on,” Nicole says. “At that point, we were desperate… His quality of life was such that the benefits outweighed the risks.”

Surgeons cut out the entire right occipital lobe and half of the temporal lobe of Collins’ brain. Those lobes are important for processing the information that passes through our eyes’ optic nerves, allowing us to see. These regions are also critical for recognizing faces and objects and attaching corresponding names. There was no way of being sure whether Collins would ever see again, recognize his parents, or even develop normally after the surgery.

And then the miraculous happened: Despite the loss of more than 15 percent of his brain, Collins turned out to be fine.

“We’re looking at the entire remapping of the function of one hemisphere onto the other.”

The one exception is the loss of peripheral vision in his left eye. Though this means Collins will never legally be able to drive, he compensates for his blind spot by moving his head around, scanning a room to create a complete picture. “It’s not like it’s blurred or it’s just black there. It’s, like, all blended,” Collins tells me when I visit him at home in January. “So, it’s like a Bob Ross painting.”

Today, Collins is a critical puzzle piece in an ongoing study of how the human brain can change. That’s because his brain has done something remarkable: The left side has assumed all the responsibilities and tasks of his now largely missing right side.

“We’re looking at the entire remapping of the function of one hemisphere onto the other,” says Marlene Behrmann, a cognitive neuroscientist at Carnegie Mellon University who has been examining Collins’ brain for more than five years.

What happened to Collins is a remarkable example of neuroplasticity: the ability of the brain to reorganize, create new connections, and even heal itself after injury. Neuroplasticity allows the brain to strengthen or even recreate connections between brain cells—the pathways that help us learn a foreign language, for instance, or how to ride a bike.

The fact that the brain has a malleable capacity to change itself isn’t new. What’s less understood is how exactly the brain does it. That’s where Behrmann’s study of Collins comes in. Her research question is twofold: To what extent can the remaining structures of Collins’ brain take over the functions of the part of his brain that was removed? And can science describe how the brain carries out these changes, all the way down to the cellular level?

Previous neuroplasticity research has shed light on how the brain forms new neuronal connections with respect to memory, language, or learning abilities. (It’s the basis for popular brain-training games meant to improve short-term memory.) But Behrmann’s research is the first longitudinal study to look closely at what happens in the brain after the regions involved in visual processing are lost through surgery or damaged due to a traumatic brain injury.

“We know almost nothing about what happens in the visual system after this kind of surgery,” she says. “I think of this as kind of the tip of the iceberg.”

So far, Behrmann’s findings are turning medical dogma on its head. They suggest that conducting brain surgeries in kids suffering seizures shouldn’t be viewed as the last available option, as it was for Collins. The surgery he underwent, while successful roughly 70 percent of the time, is still uncommon, which means that many people with similar brain tumors may be suffering unnecessarily. And depending on what Behrmann discovers, we may learn more than we ever have before about the brain’s capacity to bounce back.


The first time Collins collapsed because of a seizure, he was four and being minded by a babysitter. Over time, his symptoms grew more varied and more severe. “It’s like my brain froze,” he says. “I was really confused, and then I’d get really nauseous, throw up, and then I’d be kind of acting normal again.”

A daily ritual ensued: Collins would go to school, have a seizure, collapse, and go home. Still, despite the misery, the seizures were a blessing in disguise. They led to the discovery of the tumor slowly enveloping a piece of his brain.

“These are some of the most common tumors we see in children,” says Christina Patterson, MD, a pediatric epilepsy neurologist and part of the medical team that prepared Collins for surgery at the UPMC Children’s Hospital of Pittsburgh. “Taking out the tumor is ultimately the cure.”

The deeper problem with pediatric tumors like the one Collins developed — beyond the nausea, headaches, and confusion that he experienced — is that the seizures they produce can damage the electrical networks of the brain.

“We know that the pediatric brain has plasticity, [and] that we’re constantly creating new algorithms in the brain to live life,” Patterson says. “But when you have seizures on top of that, those disrupted electrical networks that are the seizures prevent any kind of meaningful remapping.”

Inside our brains are about 100 billion neurons. These neurons build thousands of connections with one another and communicate with their cellular brethren by converting electrical signals into chemical neurotransmitters, which are responsible for carrying information between the brain cells. As we master new skills, the brain’s neurons form new connections and strengthen old ones that aided in learning that information. Instead of discrete regions carrying out specific tasks, the brain depends on groups of neural networks talking to each other across multiple regions. (Behrmann says a single neuron can communicate with 50,000 other cells.) If the network is damaged, the brain cells can’t communicate effectively.

Picture a map of the United States that shows a phone company’s LTE network crisscrossing the country, and you have a rough approximation of how the human brain operates. Surgery for Collins, in this case, was akin to repairing a downed cell tower.

Before Collins’ surgery to remove the tumor, doctors opened up his head and placed electrodes on the surface of his brain and inside his visual cortex. For seven days, Collins lay in a hospital bed as the electrodes mapped his brain’s electrical activity, creating what was essentially a schematic diagram showing doctors where the seizures were originating and which brain areas needed to be cut out.

Collins recognized his parents after the surgery, but he couldn’t match their faces to their names. The problem resolved itself in a couple of days, but the episode left Nicole and Carl concerned: How was their son’s brain going to function with a missing part?


Consider, for a moment, a page from a Where’s Waldo? book. When your eye focuses on the crowded image, you’re actually only receiving two types of feedback: the light that falls on the retina and the color of that light. “That’s all your eye can pick up,” Behrmann says. “Yet somehow, almost instantaneously, you get an interpretation of the scene.”

Patterson put the Collins family in touch with Behrmann, who studies how brain plasticity relates to vision at her lab at Carnegie Mellon. Collins was the ideal candidate for Behrmann’s research. Children’s brains are young and still developing and therefore have the most potential for neuroplastic change. Because Collins’ tumor formed in the part of the brain crucial for visual processing, Behrmann could track his progress over time to determine whether there were any lingering deficits in his ability to interpret images. Because Collins was a child, his brain was also in a critical period of development where it builds the capacity to recognize faces, something that happens gradually and becomes more finely tuned throughout our teenage years.

As University of Toronto psychiatrist Norman Doidge notes in his 2007 book, The Brain That Changes Itself, the notion that there is a critical period of brain development is one of the most important discoveries in the area of neuroplasticity — and one for which we have kittens to thank. In the 1960s, as Doidge recounts, scientists David Hubel and Torsten Wiesel mapped the visual cortex of kittens — much in the same way Collins’ surgical team mapped his own brain — to learn how vision is processed. Then, in an admittedly grisly procedure, the scientists sewed shut the eyelid of one of the kittens in the study. Upon opening the eyelid, they found that the visual areas of the kitten’s brain responsible for processing images from that eye didn’t develop, leaving the kitten blind in that eye, even though nothing was biologically wrong with the eye. The researchers discovered that if kittens’ brains were to develop normally, they had to be able to see the world around them between their third and eighth weeks of life.

But another discovery from the study proved even more important — and earned Hubel and Wiesel the Nobel Prize. “The part of the kitten’s brain that had been deprived of input from the shut eye did not remain idle,” Doidge writes. “It had begun to process visual input from the open eye, as though the brain didn’t want to waste any ‘cortical real estate’ and had found a way to rewire itself.”

In Collins’ case, the question was whether the fully intact left hemisphere of his brain would pick up the functionality of the missing third of his brain, especially the task of facial recognition, which is typically carried out by the right hemisphere.

Collins’ left brain not only looked and performed the way his left brain should; it also looked similar in scans to other kids’ intact right brains.

Starting just before Collins was seven and continuing for three years, Behrmann administered a series of tests roughly every six months. In one challenge, he was shown photos of faces in intervals of roughly 30 seconds. If he remembered a face, he clicked a button. A similar test was administered using photos of houses, and if Collins saw the same photo back to back, he clicked a button. Each test occurred while he was inside a functional MRI machine, which allowed Behrmann to measure the flow of blood and oxygen to different regions of the brain. The more active an area of the brain, the more blood it draws.

Throughout these experiments, Behrmann compared Collins’ brain function to a control group of kids his own age without brain abnormalities. The results, published last August in Cell Reports, were striking: His neurological function was “absolutely normal,” with no subtle delays or deviations in development.

This figure shows the brain images of control groups of children around Tanner Collins’ age. The images show what normal brain development looks like at a given age. Credit: Liu et al., 2018, Cell Reports

Over coffee in the kitchen of her Pittsburgh home, Behrmann showed me successive scans of Collins’ brain that told the tale. “When he was eight, you can see the first glimmerings of face recognition in the brain,” she says. “By the time he got to 10, you can see that his left hemisphere looks really like the right hemisphere of the controls.”

In scans, Collins’ left brain not only looked and performed the way his left brain should; it also looked similar in scans as other kids’ intact right brains. That’s because the functions of the visual cortex he lost by having one-third of his right brain removed — the ability to see objects and know what they are, and the ability to recognize faces — were subsumed by his left brain. Also fascinating to Behrmann was how the left brain could accommodate two different skills: word recognition, which is the domain of the left brain, as well as facial recognition. Indeed, part of the surprise was that the left brain could keep doing what it normally does in addition to the newly added right-brain activity.

This figure is of Tanner Collins’ brain. The images show that the left hemisphere is successfully assuming the right hemisphere responsibilities that we would typically see in children his same age. The only difference here is that those responsibilities have all shifted over to Collins’ left brain. Credit: Liu et al., 2018, Cell Reports

In other words, Behrmann’s work revealed that Collins’ brain rewired itself, like the brain of the kitten that Hubel and Wiesel studied.

Just how the brain accomplishes this feat remains a central question. By analyzing brain scans using a neuroimaging technique known as diffusion tensor imaging, which shows how water travels along the brain’s white-matter tracts, Behrmann has found initial glimmerings that the white matter of the brain — the electrical wiring that underlines communication between multiple neurological regions — actually changes. Areas of the brain that weren’t connected before create new links, an example of neuroplasticity in action that may preserve brain functionality. But scientists still don’t know what triggers the cells of the white matter to behave in this way.

“When Tanner is 20, I think we’ll know a lot more about the overall wiring,” Behrmann says. “The one thing that we will not know in humans, and I don’t know how we will ever know it, are the changes that occur at the level of the cells themselves.”


Every three to six months, Collins returns to Behrmann’s lab to undergo tests and be examined for any visual deficits. Behrmann hopes that following him over time will lead to more definitive answers, not only about how his visual system finally reorganizes itself but also the process by which it does so. “We’ve got a long way to go, but the work, I think, is really exciting,” she says.

In a follow-up study Behrmann conducted with Collins and nine other children — all of whom are missing areas of either their left or right hemisphere — eight of them, including Collins, showed absolutely normal vision function. The two who did not are children whose brain damage from seizures was more severe prior to their surgeries.

This sort of insight is needed to gauge when to perform a brain surgery like the one Collins had. At what age should parents agree to remove a tumor that’s causing epileptic seizures? Sometimes, resective surgery that removes brain tissue can make it difficult for a person to use and understand words; it can also, as it did in Collins’ case, result in visual impairment.

“Once we have a better picture of exactly what happens after we remove large segments of the brain, we may be able to counsel families more effectively,” says Taylor Abel, MD, a pediatric neurosurgeon who specializes in epilepsy surgery and arrived at the Children’s Hospital of Pittsburgh last summer to begin collaborating with Behrmann. “The goal should be to do whatever you can to stop the seizures and get off of medications as early in your life as possible. The sooner you do that, the sooner you can return to a normal developmental trajectory.”

It may even be the case, Abel and Behrmann point out, that some of the reorganization that took place in Collins’ brain started prior to his scheduled surgery. It’s not something Behrmann can prove, since all the research conducted on Collins has taken place post-surgery.

“When you have an abnormality in your brain that’s causing seizures, that abnormality can actually cause the brain to reorganize or start reorganizing before the surgery actually takes place,” Abel says. “But the other thing that sometimes happens is that the seizures affect the functions in the brain, and the brain doesn’t reorganize.”

Behrmann says one of the fundamental goals of her research is to study a large enough population of children to determine if there are patterns of optimal recovery based on the age they had their surgery. Reorganization to the degree Collins has experienced is impossible for adults undergoing similar surgery, Behrmann says, as they lack the neuroplasticity seen in children.

For Nicole and Carl, the surgery was unequivocally the right decision. “What was happening before the surgery was pretty awful,” Nicole says. “After surgery, the changes were only for the better. Yeah, he has his visual deficits. But everything else was for the better.”

In late 2017, a follow-up MRI at the Children’s Hospital of Pittsburgh showed that Collins’ tumor grew back. This time, though, it was the size of a pea. Two months later, in February 2018, surgeons opened his brain a second time. Collins says the prospect of a second surgery didn’t bother him; he just wanted the pea-size tumor out of his head so he wouldn’t have to worry about it. (The surgery went well, and he’s still tumor-free.)


Aswe close in on minute 24 of our chess match, I move my king in the corner of the board, still certain of my impending doom. Collins scans his remaining white pieces and then takes a look at where his king sits.

“Mate,” he says, looking up at me.

Checkmate for me, I realize, surprised by a victory I did not expect. Collins begins breaking down the moves he made, retracing some of his steps. It seems he forgot about a pawn of mine that was still on the board.

“I like losing,” he says. “Obviously, I like winning, too. But when you lose, you gain the knowledge.”

Even after losing a portion of his brain, Collins is still learning. His brain is still growing, still adapting — and, even if it’s not readily apparent, still changing.

#A cellular safeguard against brain cancer

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© Sefa Kaya/Getty

© Sefa Kaya/Getty

 

Like a bomb squad defusing a potentially explosive suitcase, a component of the cell’s protein sorting machinery helps disarm a key signaling pathway in primitive nerve cells to prevent brain tumours from birthing.

Researchers from Peking University discovered the safeguard mechanism by studying stem cells from the developing brain of fruit flies. The Notch signalling pathway is critical for maintaining these neuroblast cells in their primitive state, and hence it must be turned off to ensure the proper development of neurons.

The researchers showed that the retromer complex — a master recycling centre for sorting molecular cargo between different membrane-bound compartments in the cell — retrieves and takes away harmful Notch receptors that could lead to abnormal dedifferentiation of neural progenitors.

The findings suggest that modulating the retromer function could offer a new treatment strategy for cancer patients, including those with aggressive brain tumours.

 

 

PKU

#Chinese Artificial Intelligence Beats 15 Doctors In Tumor Diagnosis Competition

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An AI system has wiped the floor with some of China’s top doctors when it comes to diagnosing brain tumors and predicting hematoma expansion.[​IMG]

 

As reported by Xinhua, the system defeated a team comprised of 15 of China’s top doctors by a margin of two to one. The AI, BioMind, was developed by the Artificial Intelligence Research Centre for Neurological Disorders at Beijing Tiantan Hospital, and is another example of the long line of the technology analyzing images.

When diagnosing brain tumors, BioMind was correct 87 percent of the time, compared to 66 percent by the medical professionals. The AI also only took 15 minutes to diagnose the 225 cases, while doctors took 30.

In regards to predicting brain hematoma expansion, BioMind was victorious again, as it was correct in 83 percent of cases, with humans managing only 63 percent.

Researchers trained the AI by feeding it thousands upon thousands of images from Beijing Tiantan Hospital’s archives. This has made it as good at diagnosing neurological diseases as senior doctors, as it has a 90 percent accuracy rate.

The executive vice-president of Beijing Tiantan Hospital, Wang Yongjun, told Xinhua that he didn’t care who won in the battle between doctors and the AI.

“I hope through this competition, doctors can experience the power of artificial intelligence,” he said. “This is especially so for some doctors who are skeptical about artificial intelligence. I hope they can further understand AI and eliminate their fears toward it.”

Read more at: https://forum.facmedicine.com/threads/chinese-artificial-intelligence-beats-15-doctors-in-tumor-diagnosis-competition.36291/?fbclid=IwAR3l-uHvpJTcNJ8f2GfwgDertGpOV6ObsfZCzhVNlx9CalcllhSLK74kCBA

#La ‘caja negra’ del #cerebro desvela sus primeras claves

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La comprensión de cada una de las partes de las áreas cerebrales necesita de muchos y variados enfoques y su conocimiento total se dilatará en el tiempo.

Descifrando el cerebro humano.

Imagina que vas a escalar una montaña. En la lejanía, no parece tan grande, pero cuando te vas aproximando y finalmente llegas a su ladera, te das cuenta de la inmensidad a la que te enfrentas. Este un claro ejemplo con el que Francisco Clascá, del Departamento de Anatomía y del Programa de Graduados en Neurociencias de la Universidad Autonóma de Madrid (UAM), intenta explicar la dificultad que entraña el estudio del cerebro, hecho que, lógicamente, proviene de la complejidad de las características cerebrales humanas.

“El cerebro sigue siendo un misterio y desvelar su funcionamiento total es uno de los grandes retos por alcanzar”, señala Javier de Felipe, neurocientífico del Instituto Cajal del CSIC, en Madrid. Es más, Carmen Cavada, catedrática de Anatomía Humana y Neurociencia de la Universidad Autónoma de Madrid (UAM), considera que “el cerebro humano es el gran reto de la ciencia; no sólo de la neurociencia, también de la sociología, de la pedagogía…”

Francisco Clascá:  “Ante una ingente maraña de datos, hay que establecer bases de datos con formatos y lenguajes comunes”

¿Se traducen estas consideraciones en que se ha avanzado menos de lo esperado desde que en los años noventa empezara a acuñarse la idea del comienzo de la “era del cerebro”? Ciertamente, los avances que se producen en neurociencia pueden parecer pequeños si se sopesan las patologías que se encierran en el cerebro humano, pero los investigadores consideran que en esta parcela del conocimiento se aúna el mayor el número mundial de científicos, incluidos los profesionales dedicados a la psiquiatría, neurología y neurocirugía.

Transmitir el conocimiento

En España, por ejemplo, “la neurociencia ya tiene mucha calidad y tradición”, advierte Cavada, quien introduce un nuevo punto de especial relevancia: la inversión que, en lo que se refiere a investigaciones, “no sólo debe aumentar, sino diversificarse en cuanto a su origen para poder investigar más y más”. El desarrollo de programas como el estadounidense Brain Initiative, impulsado por la anterior administración Obama, y el Brain Human Project de la UE, empiezan a aportar datos, centrados especialmente en el desarrollo de tecnologías de computación que profudicen el conocimiento cerebral. Pero, además, proyectos específicos de grupos de neurocientíficos aportan su grano de arena a la ingente producción de datos sobre áreas concretas del funcionamiento del cerebro.

En último término, los resultados de estos trabajos necesitan un punto de encuentro común que facilite la transmisión del conocimiento. “Comprender el cerebro necesita de muchos enfoques, como el estudio de la organización y funcionamiento de los circuitos y sistemas que sustentan las funciones nerviosas, sin dejar de lado aspectos que podrían aportarse si se llegara a desarrollar un genoma cerebral como ayudar a entender riesgos de sufrir ciertas enfermedades o sus mecanismos”, puntualiza Cavada.

Carmen Cavada: “El cerebro humano es el gran reto de la ciencia; no sólo de la neurociencia, sino de la sociología, de la pedagogía…”

Juan Lerma, del Instituto de Neurociencias CSIC-Universidad Miguel Hernández, de Elche, Alicante, y editor jefe de Neuroscience, redunda en la idea del actual desconocimiento de muchas de las funciones fundamentales del cerebro y de cómo se organizan, pero sí subraya dos avances, a su juicio significativos, producidos en neurociencia durante este último año.

Avances significativos

Cita, en primer término, los ensayos llevados a cabo en las universidades de Tufts y Harvard, Estados Unidos, con la aplicación de técnicas de la formación de organoides del cerebro y gracias a las cuales se han “generado mini-cerebros en 3D en una placa de andamiaje, con actividad eléctrica espontánea y que parten de células pluripotentes de la piel humana. Si estas células se obtienen de pacientes con esquizofrenia o con autismo, por ejemplo, se supone que estos mini-cerebros reproducen la enfermedad y posibilitarían analizar qué partes de la comunicación neuronal está alterada”.

Juan Lerma: “La plasticidad es una de las vías más interesantes: usar las propiedades intrínsecas cerebrales, reconducir y restaurar”

Otro de los acontecimientos que abre nuevas posibilidades investigadoras se produjo el pasado mes de noviembre (ver DM del 5-11-2018) cuando el equipo de Grégoire Courtine, de la Escuela Politécnica Federal de la Universidad de Lausana (EPFL), en Suiza, daba a conocer los resultados de la eficacia de la estimulación eléctrica en la médula espinal con neurorrehabilitación para restaurar la función, no sólo motora sino también sensitiva, en el sistema nervioso central (SNC), hecho que ha permitido caminar a tres personas parapléjicas.

El peso de la plasticidad

Para Lerma, la relevancia de estos trabajos, además de la de permitir la deambulación, es que se ha puesto de manifiesto que “una de las propiedades fundamentales del SNC, la plasticidad, puede ser usada y, de alguna manera, ‘despertada’, para reconducir y reinstaurar circuitos”. De hecho, considera que la plasticidad cerebral es una de las “avenidas de investigación más interesantes del momento: utilizar las propiedades intrínsecas del cerebro para conducir su actividad a valores normales, lo que sería de especial utilidad en autismo, esquizofrenia, trastorno bipolar o adicciones, entre otras alteraciones”, y que han sido objetivos de trabajo del equipo de Elche. En el caso de patología neurodegenerativa -Parkinson o Alzheimer, fundamentalmente- el problema es que la muerte neuronal no se recupera, aunque tal vez se podrían aprovechar los procesos de plasticidad sináptica para recomponer algunos circuitos.

Pequeñas y grandes observaciones, comprobaciones y nuevos hallazgos van desenmarañando, poco a poco, parcelas de los muchos misterios que sigue encerrando el cerebro humano. Es un reto mundial que no se resolverá a corto plazo; necesitará algunas generaciones, pero que “la Humanidad y su ciencia acabarán resolviendo”, considera Clascá. ¿Qué no daríamos todos, y muy especialmente Ramón y Cajal, por estar presentes en ese momento?

 

Enfermedad neurodegenerativa y mental

Comprender los circuitos y mecanismos que están alterados en algunas enfermedades neurodegenerativas, como el Parkinson, ha aportado beneficios tangibles para los pacientes y es una de las parcelas en las que Carmen Cavada considera que se han producido beneficios notables de la investigación en neurociencia. “Además de poder tratar la enfermedad eficazmente, en fases iniciales sobre todo, con fármacos, es posible paliar sus efectos en fases avanzadas a base de intervenciones sobre el cerebro, como la estimulación cerebral profunda o aplicación de ultrasonidos de alta frecuencia”.

No obstante, y según la catedrática, “con todo ello se consigue controlar los síntomas, pero la neurodegeneración sigue avanzando porque aún no comprendemos su causa. Este es el gran reto: comprender cómo y por qué comienza y se mantiene la neurodegeneración, ya sea en Parkinson o en Alzheimer”. Estos procesos, en su mayoría asociados al envejecimiento, impactan en la sociedad en general, pero no olvida el otro “gran reto de las enfermedades mentales”, cuyos mecanismos patogénicos parecen aún mas inalcanzables que los de las clasificadas como “neurológicas”, indica la catedrática.

#Thrombolyse intraveineuse versus traitement endovasculaire pour l’AVC ischémique aigu

Postado em

    Resultado de imagem para traitement avc thrombolyse endovasculaire

    Minerva 2013 Volume 12 Numéro 7 Page 82 – 83

     

    Analyse de
    Broderick JP, Palesch YY, Demchuk AM, et al; Interventional Management of Stroke (IMS) III Investigators. Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med 2013;368:893-903.

    Question clinique
    En cas d’AVC ischémique aigu, l’ajout d’un traitement endovasculaire après administration intraveineuse d’activateur tissulaire du plasminogène recombinant (t-PA) est-il plus efficace que l’administration seule de t-PA en termes de capacités fonctionnelles à 90 jours post incident ?

    Conclusion
    Les études IMS III, SYNTHESIS et MR-RESCUE n’ont pas montré de supériorité du traitement endovasculaire par rapport au traitement standard (thrombolyse par administration intraveineuse d’altéplase). Ces conclusions n’étayent pas l’intime conviction de beaucoup de cliniciens de la supériorité du traitement IA. Celle-ci est basée sur des « surrogate endpoints », comme un taux de recanalisation supérieur. Ces études n’ont pas suffisamment évalué la dernière génération de cathéters de thrombectomie, les stent-retrievers. Ceux-ci devraient être évalués dans des essais randomisés contrôlés, en minimisant le plus possible le délai d’intervention.

     

     

    Texte sous la responsabilité de la rédaction francophone


     

    Contexte 

    A ce jour, le seul traitement ayant prouvé son efficacité dans le traitement de l’AVC ischémique aigu est l’administration d’altéplase (t-PA) en intraveineux (IV) (1). Son grand avantage est qu’il peut rapidement être administré après examen clinique et scanner cérébral. Un traitement intra-artériel (IA) permet de recanaliser des grosses artères en occlusion, plus fréquemment et plus rapidement que l’altéplase en IV (2). Un traitement IA (seul ou en ajout) n’avait jusqu’à présent pas montré sa supériorité versus traitement par altéplase IV dans un essai randomisé contrôlé.

     

    Résumé

    Population étudiée

    • patients âgés de 18-82 ans, ayant reçu du t-PA IV < 3 heures après le début des symptômes, avec un AVC ischémique modéré à sévère (avec un National Institute of Health Stroke Scale (NIHSS) ≥ 10) au début du traitement
    • après un amendement du protocole initial, des patients avec un National Institutes of Health Stroke Scale (NIHSS) de 8-9, mais avec preuve sur CT-angiographie d’une occlusion d’une grosse artère de la base du crâne, ont pu être également inclus
    • 900 patients prévus, dans un rapport 2 (endovasculaire) à 1 (t-pA)
    • critères d’inclusion et d’exclusion correspondant à la routine clinique.

    Protocole d’étude

    • étude randomisée, en protocole ouvert, avec évaluation des critères de jugement en aveugle
    • intervention : traitement par t-PA IV suivi d’un traitement IA (IV/IA, n = 434) avec le traitement standard par t-PA IV (IV, n = 222) ; t-PA IV initié dans les 3 heures dans les 2 groupes ; traitement IA choisi par le radiologue neuro-interventionnel et pouvant comporter l’administration IA de t-PA par différents dispositifs (approuvés progressivement par la FDA et le steering comité) ; procédure angiographique devant être initiée dans les 5 heures et terminée dans les 7 heures après le début des symptômes.

    Mesure des résultats 

    • critère de jugement primaire : au jour 90, score ≤ 2 sur l’échelle de Rankin modifiée (mRS) (3), signifiant une indépendance fonctionnelle
    • critères de jugement secondaires :
      • sécurité de l’approche IV/IA par rapport au traitement t-PA IV seul : mortalité à 3 mois, hémorragie intracrânienne symptomatique confirmée par CT ou RMN
      • efficacité de l’approche IV/IA par rapport au traitement t-PA IV seul, par paramètres indirects d’efficacité comme le score TICI (Thrombolysis in Cerebral Infarction) (4) évaluant le degré de recanalisation artérielle et de reperfusion tissulaire en fin de procédure angiographique, et la perméabilité vasculaire intracrânienne à 24 heures en CT-angiographie (CTA)
    • analyse en intention de traiter.

    Résultats

    • 656 patients randomisés sur les 900 prévus pour futilité observée lors d’une analyse intermédiaire (prévue dans le protocole initial) ; 100 patients (24%) alloués au traitement IA en ajout ne l’ont finalement pas reçu, leurs résultats ne pouvant influencer les résultats moyens finaux
    • critère de jugement primaire, proportion de patients avec un mRS ≤ 2 : pas de différence statistiquement significative entre le groupe IV/IA et le groupe IV t-PA seul : 40,8% et 38,7%, différence absolue ajustée de 1,5%, avec IC à 95% de -6,1 à 9,1 ; pas de différence statistiquement significative pour les sous-groupes prédéfinis (sévérité de l’AVC, âge, présence d’une fibrillation auriculaire, rapidité du traitement)
    • critères de jugement secondaires :
      • décès, taux d’hémorragies intracrâniennes symptomatiques ou taux d’hématomes parenchymateux : pas de différence significative à 7 et à 90 jours
      • taux de recanalisation et de reperfusion en fin d’angiographie inversement corrélés avec la taille de l’artère : avec un score TICI de 2b-3 (reperfusion de ≥ 50% – 100% dans le lit vasculaire de l’artère occluse) plus de chance d’obtenir un mRS ≤ 2 à 90 jours ; taux de recanalisation en CTA à 24 heures (si mesure initiale et à 24 heures) nettement plus élevés dans le groupe IA pour les occlusions des grandes artères (artères carotide interne et cérébrale moyenne) que dans le groupe IV t-PA.

    Conclusion des auteurs 

    Les auteurs concluent à des résultats similaires en termes de sécurité et à une absence de différence significative en termes d’indépendance fonctionnelle pour l’ajout d’un traitement endovasculaire à une administration intraveineuse de t-PA versus administration intraveineuse de t-PA seule.

    Financement de l’étude

    National Institutes of Health, National Institute of Neurological Disorders and Stroke, Genentech, EKOS, Concentric Medical, Cordis Neurovascular, Boehringer Ingelheim.

    Conflits d’intérêt des auteurs

    15 des 29 auteurs déclarent avoir reçu des paiements de firmes pharmaceutiques, des autorités ou d’autres organisations ; les autres auteurs déclarent ne pas avoir de conflit d’intérêts.

     

    Discussion

    Considérations sur la méthodologie

    La nature des traitements comparés ne permet pas d’autre méthodologie que PROBE (prospective randomized, open, blinded endpoints). Lors du déroulement de l’étude, plusieurs amendements de protocole ont été approuvés, pour qu’elle reste cliniquement pertinente. En effet, pendant les 6 ans de durée de cette étude, plusieurs nouveaux types de cathéters ont été commercialisés, avec des taux de recanalisation supérieurs par rapport à ceux obtenus avec les cathéters utilisés initialement. Sans ces amendements, de plus nombreux patients auraient été traités « en ouvert », hors étude. L’amendement 3 a permis l’utilisation de la CTA afin d’inclure des patients avec un AVC un peu mois sévère, mais avec une occlusion montrée au niveau d’une grosse artère de la base du crâne. Le choix du critère de jugement primaire (mRS ≤ 2, indépendance fonctionnelle) correspond à ce que la grande majorité des cliniciens estiment comme un seuil cliniquement pertinent. Le choix des sous-groupes préalablement spécifiés est judicieux, par ce qu’il reflète un série de critères couramment utilisés en routine clinique (sévérité du déficit neurologique, l’étendue de la lésion en imagerie, rapidité du traitement, l’artère occluse, ..). Les auteurs s’en sont aussi rigoureusement tenus aux analyses statistiques préalablement protocolées et publiées.

    Interprétations des résultats

    L’efficacité d’une thrombolyse IV diminue rapidement avec le temps et est moindre en cas de thrombus important ou plus ancien. Le traitement intra-artériel (IA) permet de recanaliser les occlusions des grosses artères plus fréquemment et plus rapidement par rapport au t-PA en IV (2). Son principal désavantage est que cette procédure exige un délai plus important (rappel de l’équipe neuro-interventionnelle, transfert vers une autre institution), avec d’autres limites également : difficulté pour manœuvrer le cathéter jusqu’à l’occlusion, risque de lésion artérielle (perforation, dissection), fragmentation du caillot avec embolisation secondaire et risque lié à une anesthésie (si utilisée). Il comporte, comme le traitement IV, un risque d’hémorragie cérébrale. Le t-PA IV, suivi d’un traitement IA combine l’avantage d’une instauration rapide du traitement avec une probabilité plus grande de recanalisation en cas d’occlusion persistante après le traitement IV.

    Les résultats de cette étude sont une grande déception pour les adeptes du traitement endovasculaire. En effet, la plupart des AVC sont le résultat d’une occlusion artérielle d’origine thrombotique ou embolique. Le but du traitement de l’AVC aigu est donc de recanaliser le plus vite possible cette artère afin de reperfuser le territoire à risque. Pour le seul traitement approuvé pour l’AVC ischémique aigu, le t-PA administré endéans les 4,5 heures après le début des symptômes, des taux de recanalisation faibles, en moyenne de 40%, ont toujours été rapportés. Les taux de recanalisation dans cette étude-ci étaient nettement plus élevés dans le groupe endovasculaire que dans le groupe IV t-PA, néanmoins le résultat fonctionnel à 3 mois n’était pas meilleur. Cette observation trouve probablement son explication dans le fait qu’une recanalisation d’une artère n’apporte pas de bénéfice si elle a lieu trop tard, c’est-à-dire quand le tissu est déjà infarci. Néanmoins, l’étude IMS III ouvre des perspectives pour de futures études. Bien que statistiquement non-significatifs, les résultats de l’analyse des sous-groupes suggèrent un bénéfice si le t-PA IV est administré dans les 2 heures avec un traitement endovasculaire suivant dans les 90 minutes.

    Autres études

    Dans la même semaine, 2 autres études évaluant le traitement IA ont été publiées : SYNTHESIS (5) et MR-RESCUE (6). La première, comparant un traitement IA avec le t-PA IV, a inclus 362 patients (181 IV et 181 IA). Contrairement à IMS III, des patients avec un déficit léger (pas de limitations du score NIHSS) ont également été inclus. Dans le groupe IV, le traitement a été administré en moyenne 2,75 heures après le début des symptômes et dans le groupe IA 3,75 heures après le début. Cette étude montre que le traitement endovasculaire n’est pas supérieur au traitement IV pour le critère de jugement primaire (mRS ≤ 1 : pas de handicap fonctionnel malgré des symptômes neurologiques). MR-RESCUE se différencie des 2 autres études par une imagerie cérébrale plus poussée pour identifier un profil de pénombre favorable (une petite zone centrale irrévocablement infarcie et une grande zone périphérique potentiellement récupérable, la pénombre) ou défavorable. L’espoir était d’identifier des patients qui pourraient bénéficier d’un traitement IA au-delà des 4,5 heures établies. La thrombectomie n’est pas supérieure au traitement standard pour le critère de jugement primaire (mRS ≤ 2), pour les 2 groupes de patients (profil favorable, profil défavorable). Il n’y avait donc pas d’interaction entre le profil d’imagerie et le traitement assigné.

     

    Conclusion de Minerva

    Les études IMS III, SYNTHESIS et MR-RESCUE n’ont pas montré de supériorité du traitement endovasculaire par rapport au traitement standard (thrombolyse par administration intraveineuse d’altéplase). Ces conclusions n’étayent pas l’intime conviction de beaucoup de cliniciens de la supériorité du traitement IA. Celle-ci est basée sur des « surrogate endpoints », comme un taux de recanalisation supérieur. Ces études n’ont pas suffisamment évalué la dernière génération de cathéters de thrombectomie, les stent-retrievers. Ceux-ci devraient être évalués dans des essais randomisés contrôlés, en minimisant le plus possible le délai d’intervention.

     

    Pour la pratique

    A l’heure actuelle, un traitement endovasculaire n’a pas montré de supériorité par rapport au t-PA IV pour le traitement de l’AVC aigu qui reste recommandé < 4,5 heures après le début des symptômes d’AVC (1). Un traitement endovsculaire ne peut être envisagé qu’en cas de contre-indication à la thrombolyse IV. Pour tous les autres patients, ce procédé ne devrait être réalisé que dans le cadre de technique d’études randomisées contrôlées.

     

    Références

    1. Wardlaw JM, Murray V, Berge E, et al. Recombinant tissue plasminogen activator for acute ischaemic stroke: an updated systematic review and meta-analysis. Lancet 2012;23;379:2364-72.
    2. Meyers PM, Schumacher HC, Connolly ES Jr, et al. Current status of endovascular stroke treatment. Circulation 2011;123:2591-601.
    3. Quinn TJ, Dawson J, Walters MR, Lees KR. Functional outcome measures in contemporary stroke trials. Int J Stroke 2009;4:200-6.
    4. Tomsick T, Broderick J, Carrozella J, et al; Interventional Management of Stroke II Investigators. Revascularization results in the Interventional Management of Stroke II trial. AJNR Am J Neuroradiol 2008;29:582-7.
    5. Ciccone A, Valvassori L, Nichelatti M, et al; SYNTHESIS Expansion Investigators. Endovascular treatment for acute ischemic stroke. N Engl J Med 2013;368:904-13.
    6. Kidwell CS, Jahan R, Gornbein J, et al; MR RESCUE Investigators. A trial of imaging selection and endovascular treatment for ischemic stroke. N Engl J Med 2013;368:914-23.

    #Nova descoberta com fármaco poderá travar cancro do cérebro

    Postado em

    Fonte de imagem: upi

    Uma equipa de investigadores poderá ter encontrado uma solução para travar a evolução do glioblastoma, a forma de cancro do cérebro mais fatal, com um novo método de tratamento e fármaco, indicou um estudo.

    Os tecidos no nosso corpo são maioritariamente constituídos por líquido. O líquido movimenta-se à volta das células e é fundamental para uma função normal do organismo.

    No entanto, em certos casos, poderá não ser bem assim.

    Nos doentes com glioblastoma, este fluído, denominado intersticial, fica com uma pressão maior, o que o faz circular mais rapidamente, forçando as células cancerígenas a espalharem-se.

    Os investigadores da Faculdade de Engenharia do Instituto Tecnológico da Virgínia, EUA, liderados por Jennifer Munson, analisaram, em ratinhos de laboratório, o efeito de um método de tratamento do cancro, conhecido como “entrega por convecção reforçada” (que consiste em aplicar o fármaco diretamente no tumor), sobre a invasão das células gliais para o resto do cérebro.

    A equipa descobriu que, ao usarem um fármaco conhecido como AMD3100, era possível bloquear a rapidez de circulação do fluído intersticial e, assim, a invasão das células cancerígenas. O fármaco AMD3100 já é usado no contexto clínico.

    Segundo Chase Cornelison, autor principal do estudo, este achado poderá eventualmente impedir que o glioblastoma se espalhe para o resto do cérebro.

    “Tenho esperança, considerando que o fármaco que usámos para bloquear a estimulação do fluxo é usado atualmente em pacientes, que os médicos, quando considerarem usar a entrega por convecção reforçada, talvez a combinem com este fármaco”, comentou o investigador.

     

     

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