This transcript has been edited for clarity.
Dear colleagues, I'm Christoph Diener from the medical faculty of the University Duisburg-Essen in Germany. In this video, I would like to summarize my subjective selection of the 12 most important studies and publications in 2024.
Alzheimer’s Disease and Dementia
Let me start with dementia and Alzheimer's disease. The Lancet Commission on dementia published a great review paper on all aspects of dementia. They identified 14 potentially modifiable risk factors and comorbidities that have an impact on either the incidence or progression of, for example, Alzheimer's disease and dementia.
At the same time, we have now, for the first time, approved therapies, monoclonal antibodies against beta amyloid for the early stages of Alzheimer's disease. This therapy is very expensive — expensive in terms of initial diagnosis, using the therapy, follow-up, and so on. I ask myself whether this money would not be much better spent in setting up community health centers in areas that have a high risk for dementia and provide people there with education from nurses to identify and to treat modifiable risk factors in a good fashion.
My next topic is, again, dementia, and it is the possible association of herpes zoster infection and dementia. There are population-based studies that indicate that herpes zoster infection increases the risk for dementia by about 20%. We also have data from observational population-based studies that vaccination against herpes zoster might decrease this risk. A recent study showed that recombinant vaccines are more effective in this respect than the live vaccines that were used in the past.
Long COVID
Another topic is long COVID. This was, for a long time, a controversial issue, and now a number of health authorities accepted this as a new disease and diagnosis. We now have large studies showing that there are many differences between people with and without long COVID in terms of proteomics, and in particular, in the area of cytokines.
GIP/GLP-1s and Biomarkers
The combined GIP/GLP-1 agonists, like tirzepatide, are clearly effective in diabetes mellitus and obesity. Two new studies have shown that this drug is also effective in obstructive sleep apnea syndrome. This is, interestingly, independent of the weight loss. Now there is obviously a new treatment for sleep apnea disorders.
Biomarkers play a more and more important role in a number of inflammatory and degenerative neurologic diseases. One example is multiple sclerosis, where we now have a number of interesting biomarkers. A research group in Münster, Germany, identified people with early multiple sclerosis and followed them for 4 years. Then they created clusters of a large number of biomarkers to identify three specific endophenotypes with typical immune signatures.
One of these phenotypes, for example, predicted whether patients would respond to beta interferon or not. I think in the future, this is the end of single biomarkers. We will need to use very complicated immune signatures to identify patients who might respond differently to different treatments for multiple sclerosis.
Parkinson’s Disease
As you know, all studies on neuroprotective therapy in Parkinson's disease failed. This could partly be due to the fact that, once a disease shows symptoms, it's too late to treat. In The Lancet, there were two important classification papers for identifying people in the preclinical stage of Parkinson's disease. The features that are proposed are genetics like whole-genome sequencing; the detection of alpha-synuclein, for example, in skin biopsy, CSF, or serum; the evidence of neurodegeneration in imaging; and preclinical symptoms, such as REM sleep disturbances, olfactory disturbances, and constipation.
In this context, there was a spectacular report of two patients with REM sleep disturbance in the prodromal phase of incipient Parkinson's disease. Both patients were treated with acetyl-DL-leucine and their REM sleep disorder improved, and in parallel, interestingly, the metabolic brain functional imaging improved. This would be the first time that one treatment could have an effect on the progression of Parkinson's disease. This has to be investigated in large, randomized, placebo-controlled trials.
Migraine and Glioblastoma
Let me move to migraine. The British Medical Journal published a paper on 137 studies, a meta-analysis, which looked at the treatment of acute migraine and the primary endpoint of 2 hours pain free. The reference substance was sumatriptan. The study showed that eletriptan and rizatriptan are clearly more effective than sumatriptan, and the new migraine drugs, lasmiditan and rimegepant, are less effective. The most important aspect of this study is that eletriptan is very rarely prescribed for people with acute migraine attacks.
We have new treatments for the prevention of migraine, and these are the monoclonal antibodies against CGRP. There is a new approach, and these are antibodies against PACAP, which also plays a role in the pathophysiology of migraine. A proof-of-concept study showed that an antibody against PACAP can reduce the number of migraine days. This was a short period, so now this has to be tested in a large-scale trial.
How can we find new drugs that work in glioblastoma? There's an interesting study from Zurich, Switzerland. These people collected tumor tissue samples from 27 human glioblastomas and cultured them. Subsequently, they performed chemosensitivity testing of 132 drugs on tumor cells and nontumor cells.
The substances that were working on the tumor cells were validated in in vivo models. One of these drugs that seems to work is vortioxetine, which is an antidepressant drug. We are looking forward to large-scale studies, hopefully, which will investigate this drug in human glioblastoma.
Stroke Therapy
Finally, let me come to stroke. We have now 11 studies comparing tenecteplase and alteplase for thrombolytic therapy in acute ischemic stroke. A meta-analysis showed a small benefit of tenecteplase over alteplase, but there was no difference for mortality and the risk for bleeding. Tenecteplase has the advantage that it's given as a bolus and it's particularly useful for people who are transported to a thrombectomy center, but it's also a little bit more expensive.
In the meantime, we have 16 randomized and observational studies on the efficacy and safety of endovascular thrombectomy in patients with large ischemic stroke. In this population, there is a benefit of thrombectomy in terms of functional outcome. There is no increased risk for bleeding; therefore, we can now offer thrombectomy as a very effective treatment for a large range of patients with stroke.
Dear colleagues, I'm Christoph Diener from the medical faculty of the University of Duisburg-Essen in Germany. These were my 12 most important studies and publications in 2024. Thank you very much for listening and watching.
COMMENTARY
Diener’s Top 12 Neurology Stories in 2024
Hans Christoph Diener, MD, PhD
DISCLOSURES
| December 20, 2024This transcript has been edited for clarity.
Dear colleagues, I'm Christoph Diener from the medical faculty of the University Duisburg-Essen in Germany. In this video, I would like to summarize my subjective selection of the 12 most important studies and publications in 2024.
Alzheimer’s Disease and Dementia
Let me start with dementia and Alzheimer's disease. The Lancet Commission on dementia published a great review paper on all aspects of dementia. They identified 14 potentially modifiable risk factors and comorbidities that have an impact on either the incidence or progression of, for example, Alzheimer's disease and dementia.
At the same time, we have now, for the first time, approved therapies, monoclonal antibodies against beta amyloid for the early stages of Alzheimer's disease. This therapy is very expensive — expensive in terms of initial diagnosis, using the therapy, follow-up, and so on. I ask myself whether this money would not be much better spent in setting up community health centers in areas that have a high risk for dementia and provide people there with education from nurses to identify and to treat modifiable risk factors in a good fashion.
My next topic is, again, dementia, and it is the possible association of herpes zoster infection and dementia. There are population-based studies that indicate that herpes zoster infection increases the risk for dementia by about 20%. We also have data from observational population-based studies that vaccination against herpes zoster might decrease this risk. A recent study showed that recombinant vaccines are more effective in this respect than the live vaccines that were used in the past.
Long COVID
Another topic is long COVID. This was, for a long time, a controversial issue, and now a number of health authorities accepted this as a new disease and diagnosis. We now have large studies showing that there are many differences between people with and without long COVID in terms of proteomics, and in particular, in the area of cytokines.
GIP/GLP-1s and Biomarkers
The combined GIP/GLP-1 agonists, like tirzepatide, are clearly effective in diabetes mellitus and obesity. Two new studies have shown that this drug is also effective in obstructive sleep apnea syndrome. This is, interestingly, independent of the weight loss. Now there is obviously a new treatment for sleep apnea disorders.
Biomarkers play a more and more important role in a number of inflammatory and degenerative neurologic diseases. One example is multiple sclerosis, where we now have a number of interesting biomarkers. A research group in Münster, Germany, identified people with early multiple sclerosis and followed them for 4 years. Then they created clusters of a large number of biomarkers to identify three specific endophenotypes with typical immune signatures.
One of these phenotypes, for example, predicted whether patients would respond to beta interferon or not. I think in the future, this is the end of single biomarkers. We will need to use very complicated immune signatures to identify patients who might respond differently to different treatments for multiple sclerosis.
Parkinson’s Disease
As you know, all studies on neuroprotective therapy in Parkinson's disease failed. This could partly be due to the fact that, once a disease shows symptoms, it's too late to treat. In The Lancet, there were two important classification papers for identifying people in the preclinical stage of Parkinson's disease. The features that are proposed are genetics like whole-genome sequencing; the detection of alpha-synuclein, for example, in skin biopsy, CSF, or serum; the evidence of neurodegeneration in imaging; and preclinical symptoms, such as REM sleep disturbances, olfactory disturbances, and constipation.
In this context, there was a spectacular report of two patients with REM sleep disturbance in the prodromal phase of incipient Parkinson's disease. Both patients were treated with acetyl-DL-leucine and their REM sleep disorder improved, and in parallel, interestingly, the metabolic brain functional imaging improved. This would be the first time that one treatment could have an effect on the progression of Parkinson's disease. This has to be investigated in large, randomized, placebo-controlled trials.
Migraine and Glioblastoma
Let me move to migraine. The British Medical Journal published a paper on 137 studies, a meta-analysis, which looked at the treatment of acute migraine and the primary endpoint of 2 hours pain free. The reference substance was sumatriptan. The study showed that eletriptan and rizatriptan are clearly more effective than sumatriptan, and the new migraine drugs, lasmiditan and rimegepant, are less effective. The most important aspect of this study is that eletriptan is very rarely prescribed for people with acute migraine attacks.
We have new treatments for the prevention of migraine, and these are the monoclonal antibodies against CGRP. There is a new approach, and these are antibodies against PACAP, which also plays a role in the pathophysiology of migraine. A proof-of-concept study showed that an antibody against PACAP can reduce the number of migraine days. This was a short period, so now this has to be tested in a large-scale trial.
How can we find new drugs that work in glioblastoma? There's an interesting study from Zurich, Switzerland. These people collected tumor tissue samples from 27 human glioblastomas and cultured them. Subsequently, they performed chemosensitivity testing of 132 drugs on tumor cells and nontumor cells.
The substances that were working on the tumor cells were validated in in vivo models. One of these drugs that seems to work is vortioxetine, which is an antidepressant drug. We are looking forward to large-scale studies, hopefully, which will investigate this drug in human glioblastoma.
Stroke Therapy
Finally, let me come to stroke. We have now 11 studies comparing tenecteplase and alteplase for thrombolytic therapy in acute ischemic stroke. A meta-analysis showed a small benefit of tenecteplase over alteplase, but there was no difference for mortality and the risk for bleeding. Tenecteplase has the advantage that it's given as a bolus and it's particularly useful for people who are transported to a thrombectomy center, but it's also a little bit more expensive.
In the meantime, we have 16 randomized and observational studies on the efficacy and safety of endovascular thrombectomy in patients with large ischemic stroke. In this population, there is a benefit of thrombectomy in terms of functional outcome. There is no increased risk for bleeding; therefore, we can now offer thrombectomy as a very effective treatment for a large range of patients with stroke.
Dear colleagues, I'm Christoph Diener from the medical faculty of the University of Duisburg-Essen in Germany. These were my 12 most important studies and publications in 2024. Thank you very much for listening and watching.
Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
TOP PICKS FOR YOU