ANKLE FRACTURE: Determining stability remains a diagnostic dilemma

 This team of orthopedic surgeons from the Miller School of Medicine at the University of Miami provide us here with their protocols for better management of common ankle fractures. Although relatively common, the management of an isolated fracture of the malleolus remains indeed a challenge for orthopedic surgeons. In particular, it is a question of determining whether a surgical or non-surgical intervention is indicated, in a personalized way for each patient.

 

The stability or not of the ankle depends on several factors, the authors remind: especially since no clinical or imaging examination appears to be clearly superior in determining the stability of the ankle after an injury, adds Dr Amiethab A Aiyer, an orthopedic surgeon specializing in foot and ankle care, at Miller School of Medicine. His team sought to convey their experience and available treatment options to clinicians and patients. In particular on the management of isolated lateral malleolus fractures. The malleolus are the bony structures located on each side of the ankle.

 

• Below the level of syndesmosis: In general, non-surgical treatment is indicated when an ankle is stable after injury. This is particularly the case in the case of a Weber A fracture, a type of ankle fracture characterized by relatively good ankle stability (according to the Danis-Weber classification). Weber A fractures occur below the level of the joint connecting the tibia and fibula bones, also called the level of the syndesmosis.
• When the lesion occurs above the syndesmosis , the fracture, Weber C tends to be more unstable and requires surgery.
• Between the two, a gray area?Indeed, the question arises for Weber B fractures occurring at the level of the syndesmosis. Their management remains much less clear, and this is the subject of this study. The surgeon authors then recommend evaluating the medial space cleared on the radiographs in order to determine the presence of a lesion in the medial flank. In general, a wider gap signals less ankle stability after a fracture. In addition, the authors recommend that clinicians take into account the severity of patients' pain to guide their clinical management. Again, they stress in their press release, “stability is at the heart of the assessment”. But they also recognize that “determining ankle stability after an isolated lateral malleolar fracture remains a diagnostic dilemma”.

 

It should be noted that the assessment of stability is at the heart of the therapeutic decision but here, dynamic imaging with stress radiographs remains the standard practice for detecting tibio-talar instability. But again, the authors recommend choosing the imaging approach best suited to each patient. Weight-bearing radiographs may vary depending on the weight placed by the clinician, but should incorporate the inherent stability of the ankle in a neutral position. "  If the patient is able to put weight on their ankle and there is no radiographic evidence of deltoid involvement, the ankle injury is usually stable and does not require surgery  ."

 

The team will now work on comparing the results obtained with the different technologies available, including the different plate options (thinness, new materials, nailing devices) including the cost/benefit ratio.

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STEM CELLS and CNS: The biodegradable scaffold that facilitates transplantation

 It is a new step that has just been taken in new technologies for stem cell therapy of diseases and traumas of the central nervous system (CNS) with this biodegradable scaffold, developed by a team from Rutgers University (New Jersey ) and featured in the journal Nature Communications. This new nano-device reduces the slowness of the scaffold degradation process and allows for improved grafting, differentiation and drug delivery from stem cells.

 

Stem cell transplantation is a promising therapeutic avenue for diseases of the central nervous system (CNS), it induces stem cells to become neurons and thus aims to restore neuronal circuits. However, the therapy still has to overcome multiple challenges, including low cell survival rate, partial differentiation of grafted cells, and limited growth of neurites or neuron extensions. Faced with these obstacles, scientists have developed biocells that mimic the microenvironment of natural tissues to produce physical and soluble signals. However, the bulk drug release, cell adhesion, and scaffold degradation rate remain to be optimized.

 

This biodegradable nano-scaffold (see visual) designed by Rutgers scientists is made of stem cells, proteins and drugs, intended for advanced stem cell therapy and drug delivery. It is a valuable and promising prototype for treating Alzheimer's and Parkinson's disease, age-related cognitive impairment, spinal cord injury and brain trauma.

 

A proof of concept in vitro and in vivo: the scaffolding which imitates natural tissues obtains good results here in vitro and after transplantation in mice. The researchers, in cooperation with neuroscientists and clinicians, plan to test the nano-scaffolds in larger animals and eventually move into clinical trials to treat spinal cord injuries.

 

Scaffold-based technology also shows promise in regenerative medicine.

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ACQUIRED EPILEPSY: Identification of the key role of perineuronal networks

 According to the World Health Organization (WHO), more than 50 million people worldwide suffer from epilepsy. About a third of these people do not respond to current antiepileptic treatments. It's a century-old mystery of neuroscience that these Virginia Tech scientists solve here: the research team indeed identifies mysterious brain structures called perineuronal networks, which help modulate the activity of electrical impulses in the brain. New findings, presented in the journal Nature Communications, that may lead to the treatment of epileptic disease, far beyond just managing its main symptoms, seizures.

 

In 1893, the Virginia researchers explain, scientists discovered the existence of enigmatic structures called perineuronal networks wrapped around neurons, but their function remained misunderstood. The team figured out that these networks modulate electrical impulses in the brain. And if by misfortune these networks are eliminated or malfunction, crises can then occur.

 

The implications relate to the different forms of acquired epilepsy, resulting from brain damage caused by trauma, infection, or brain tumors. The researchers began by studying tumor-associated epilepsy in a mouse model of glioblastoma-induced epilepsy. As the skull prevents the glioblastoma from spreading outward, the tumor produces an excitatory neurotransmitter called glutamate, in excessive amounts, which kills nearby healthy cells to allow its growth. And, in addition to glutamate, the tumor secretes an enzyme aimed at destroying the surrounding extracellular matrix, a gel-like substance that holds brain cells in place. This enzyme, explains the author, “is the knife that cuts the links of the tumor and lets it migrate freely”. The researchers find, surprisingly, that the enzyme attacks the perineuronal networks wrapped around inhibitory neurons secreting GABA, which normally helps prevent seizures. Once the neurons are stripped of these networks, a “crisis” effect develops.

 

An enzyme that can devour a perineuronal network in less than 30 minutes: neurons covered in perineuronal networks have reduced membrane capacity or electrical charge storage capacity, which means they can trigger an impulse and recharge twice as much faster than neurons without perineuronal networks. When inhibitory neurons lose their perineuronal networks, the results can be catastrophic. So when researchers apply the enzyme to tumor-free brains, they find that enzymatic degradation of perineuronal networks is sufficient to induce seizures. Thus, without the perineuronal networks, the inhibition becomes too weak and the seizure occurs.

 

The discovered enzyme as well as the perineuronal networks appear here as possible targets in different forms of acquired epilepsy and could allow the development of new pharmacological solutions aimed at controlling tumor-associated seizures or other causes of acquired epilepsy.  

Thus, while controlling the symptoms of the disease is important in the management of epilepsy, this study opens a new avenue for treating the causes and progression of the disease.

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