Revolutionary neurodegeneration treatment, antibiotics for dementia, and cough syrup for Parkinson disease
We get it. The overwhelming amount of new neuro research is enough to get your head spinning (pun intended), but that shouldn’t stop you from keeping up-to-date on all the latest neuro news. With researchers studying antibiotics as a possible treatment for dementia, cough syrup proving effective in treating Parkinson disease, ultrasound being used to treat neurodegeneration, and even the possibility of an Alzheimer disease vaccine, there’s just too much to miss.
Founded in 1920 by Harvey Cushing, MD, the Society of Neurological Surgeons (SNS) is the oldest neurosurgical professional society in the world and was fundamental in establishing neurological surgery as an independent medical specialty. One of the primary objectives of the SNS is to liaise with other chief neurological surgery organizations involved in resident education in North America to determine the content and format of residency and fellowship education with respect to curriculum requirements and program design.
In the News
Serotonin has a hand in neuroregeneration. In zebrafish models of Alzheimer disease, researchers found that amyloid-induced interleukin-4 (IL-4) promoted neurogenic stem cell proliferation via the suppression of serotonin production. This activity occurred in the brain’s hypothalamic core region. In zebrafish, dying neurons excrete IL-4, which activates microglia and increases neural stem cell proliferation. The researchers’ findings provide greater insight into how the serotonergic system controls many areas of neuroregeneration.
What area of the brain is known as the ‘pace-maker’ or ‘clock of the brain’?
The suprachiasmatic nucleus is considered the brain’s circadian clock. It regulates internal systems and synchronizes them to the changes in the body’s state and changes in the cycles of day and night. In other words, it is the master of all of the circadian rhythms in the body.
Epworth Sleepiness Scale just isn’t enough. In measuring excessive daytime sleepiness (EDS), the Epworth Sleepiness Scales (ESS) may not be enough. Researchers found that feelings of sleepiness better reflected sleep-related symptoms and quality of life than ESS scores, which are commonly used to measure EDS. Thus, they recommended clinicians measure both the feeling of sleepiness and the risk of dozing off in diagnosing EDS in patients. However, they also found that reporting only the risk of dozing off without feeling sleepy may not be a good reflection of sleep problems. They concluded that when evaluating daytime sleepiness, more tools are needed in addition to the ESS.
Better ‘spin’ for diagnosis of mild cognitive impairment? Arterial spin labeled perfusion MRI (ASL-MRI) may be a noninvasive, viable alternative to 18F-FDG-PET in the diagnosis of mild cognitive impairment in older adults. 18F-FDG-PET measures glucose metabolism and is one of the most commonly used biomarkers for neurodegeneration. It’s expensive, however, and requires a radioactive tracer and exposure to ionizing radiation. ASL-MRI quantifies cerebral blood flow, which may be linked to glucose metabolism. Researchers found that the patterns and strength of ASL hypoperfusion and FDG-PET hypometabolism in patients with mild cognitive impairment were comparable. This is great news for the diagnosis and measurement of disease progression in patients with Alzheimer disease!
A simple, accurate, noninvasive way to distinguish neurodegenerative disorders? Transcranial magnetic stimulation (TMS) may be a great way to classify and distinguish neurodegenerative disorders, according to researchers from Italy. They enrolled 694 participants, of whom 273 had Alzheimer disease, 67 had dementia with Lewy bodies, 207 had frontotemporal dementia, and 147 were healthy volunteers. Patients underwent TMS, and their results were compared with those from healthy controls. TMS reliably and selectively distinguished all of these conditions, with high classification accuracy and high F1 scores. Check!
A new treatment option for sialorrhea. RimabotulinumtoxinB—commonly known as botulinum toxin type B—may reduce sialorrhea in adults, according to a new study in JAMA Neurology. Researchers studied 187 patients with sialorrhea caused by Parkinson disease, stroke, amyotrophic lateral sclerosis, medication, cerebral palsy, and other etiologies. Patients had a minimum unstimulated salivary flow rate of 0.2 g/min and a minimum Drooling Frequency and Severity Scale score of 4. They were randomized to either 2,500- or 3,500-U doses of rimabotulinumtoxinB or placebo. At week 4, Clinical Global Impression of Change scores were significantly improved in both treatment groups vs placebo groups, and rimabotulinumtoxinB injections brought about benefits as soon as week 1 (treatment effect: -0.30 for both doses; P < 0.001). These results were maintained over the 13-week treatment cycle. Injections were well tolerated, and the most common adverse events included self-limited mild to moderate dry mouth, dysphagia, and dental caries. A good step towards improving quality of life and physical well-being of patients!
Cough syrup for Parkinson disease? Safely used as a cough syrup since the 1970s, ambroxol now holds potential as a treatment for Parkinson disease (PD). Here’s why: GBA1 mutations are the most important risk factor for PD. These mutations are associated with increased ɑ-synuclein accumulations, which, in turn, have a reciprocal relationship with beta-glucocerebrosidase (GCASE) enzyme activity. GCase activity is not only reduced in PD patients with and without GBA1 mutations, but also in cerebrospinal fluid (CSF). Upregulation of GCase activity could lower ɑ-synuclein levels and have a neuroprotective effect on PD patients. In a nonrandomized, noncontrolled trial, ambroxol crossed the blood-brain barrier and increased CSF ɑ-synuclein concentrations by 13% (P = 0.01) and CSF GCase protein levels by 35% (P = 0.002). Study researchers called for placebo-controlled clinical trials on the association of ambroxol therapy within the natural progression of PD.
Antibiotics for dementia? Great news for patients with dementia who currently have no treatment options: Aminoglycosides could become an effective treatment for frontotemporal dementia. Some people with this type of dementia have a specific gene mutation that prevents the production of progranulin, a protein produced by brain cells. In a proof-of-concept study, researchers found that adding aminoglycoside antibiotics to neuronal cells with the mutation caused the mutation to skip, and cells made full-length progranulin proteins. In other words, the antibiotics tricked the cells into producing the missing protein! Researchers also found that gentamicin and G418—two aminoglycoside antibiotics—were both effective, causing a 50% to 60% recovery in progranulin protein levels.
A revolutionary treatment for neurological disorders. A new, noninvasive ultrasound technique—transcranial pulse stimulation (TPS) with ultrasound—may make it possible to activate neurons throughout the brain that can regenerate brain functions. Researchers from MedUni Vienna spent 6 years developing this new treatment—the first of its kind. According to their preliminary data, this ultrasound-based method can improve brain performance by emitting a stimulating pulse between 3 and 5 mm wide and approximately 3 cm long to precise areas of the brain as mapped by MRI. These TPS pulses cause short-term membrane changes in the brain cells, which bring about neuronal activation and compensatory networks development to improve whatever brain functions are affected. Researchers found that the memory network can be boosted, and memory performance can be improved. In fact, six 1-hour sessions delivered over 2 weeks were enough to improve brain performance. Potential TPS applications include Alzheimer and Parkinson diseases, and multiple sclerosis. If their results are confirmed, TPS could completely change how we treat neurological disorders.
New in Patient Management
Need a crystal ball to predict seizures in in-patients? Nope. All you need is the 2HELPS2B score. Among hospitalized patients, the 2HELPS2B score could be a great aid in detecting seizures, improving clinical communications, and determining the optimal use of continuous EEG (cEEG). The 2HELPS2B score is based on six readily available seizure risk factors from a patient’s history and cEEG monitoring. The score has been shown to accurately predict seizures in acutely ill hospitalized patients. After studying 2,111 patients with clinical indications for cEEG and EEGs of 12 hours or longer, researchers recommended that patients who exhibited any highly epileptiform EEG patterns during the first hour of EEG (with a 2HELPS2B score of 2 or more) be recorded for at least 24 hours. In patients with no previous clinical seizures, however, a 1-hour screening EEG with no epileptiform findings may be adequate evidence that the patient is at low risk of seizures for at least the next 72 hours.
Antipsychotics bad for Alzheimer’s patients? People with Alzheimer disease taking antipsychotic medications may be at an increased risk of head injuries, according to a recent study. In a large Finnish cohort of over 43,000 patients, the use of antipsychotics was linked to a 29% increased risk of head injuries and a 22% increased risk of traumatic brain injuries (TBIs). Furthermore, those who used the antipsychotic quetiapine had a 60% higher risk of TBIs compared with those who took risperidone. Researchers stressed that because these patients already have a higher risk of falls, head and brain injuries, and worse prognosis, treatment with antipsychotics should be carefully considered and perhaps avoided.
A vaccine against Alzheimer disease? Yes, please. Last week we reported on a vaccine for dementia. It’s only getting better from there. Researchers are now one step closer to developing a vaccine for Alzheimer disease (AD). Hard to believe, right? Bacillus Calmette-Guérin (BCG) therapy—developed as a vaccine against tuberculosis—was shown to significantly reduce the risk of developing AD in patients with bladder cancer. The vaccine was previously shown to modulate the immune system and reduce the recurrence of non-muscle invasive bladder cancer. Researchers did a retrospective study in 1,371 patients with bladder cancer and found that patients treated with BCG had a more than 4-times less risk of AD compared with those not vaccinated. But BCG vaccination had no effects on the prevalence of Parkinson disease. Imagine the possibilities!
Help predicting outcomes in status epilepticus. In a prospective study, researchers tested the abilities of the Epidemiology-based Mortality score in Status Epilepticus (EMSE) and the Status Epilepticus Severity Score (STESS) performance to predict outcomes in patients with status epilepticus. They found that these patients have a greater than 40% adverse outcome rate. Furthermore, they concluded that the EMSE-EAC (ESME with combined etiology, age, comorbidity) and STESS are useful in predicting short-term mortality. They determined that the optimal cut-off points for both of these tests were ≥ 34 and ≥ 4, respectively. Many patients with status epilepticus suffer adverse outcomes, but these simple tests will help physicians better predict which patients are at risk.
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Upcoming Medical Meetings
46th Annual Meeting of the Southern Clinical Neurological Society (SCNS) CME, in Naples, FL, January 18-22, 2020
13th Annual Headache Cooperative of the Pacific (HCOP) Winter Conference CME, in Ojai, CA, January 24-25, 2020
12th Annual Symposium on Neurovascular Disease CME, in Santa Monica, CA, January 25, 2020
North American Neuromodulation Society (NANS) Annual Meeting CME, in Las Vegas, NV, January 23-26, 2020