The effects of smoking & alcohol on the brain, a neuroprotective glycoprotein, and a less invasive spinal injection technique

We’re only half-way into February and yet there’s already so much new, important neuroscience research to cover. There’s great neurology news from every direction, with a spin on the old and a firm grasp of the new.

Researchers have shown that an older drug—granulocyte-colony-stimulating factor (GCSF)—may offer neuroprotection against autophagy and mitochondrial stress, marking it as a promising novel treatment for stroke. And, new approaches to old problems are also in the spotlight. For example, a team of international researchers, led by UCSD scientists, are testing a new, less invasive injection technique for the repair of spinal cord injuries. Even more exciting? It seems that the mind-body connection may grow stronger at every turn. Researchers found structural changes in the corticospinal tracts of patients who underwent anterior cruciate ligament (ACL) reconstruction, demonstrating that even the knee is connected to the brain! So many interesting new findings to catch up on! Keep reading for more.

Neuro Flashback

In 1952—nearly 70 years ago—the American Psychiatric Association published the first edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM). Now in its fifth edition, the DSM is the definitive reference used by clinicians and psychiatrists to diagnoses psychiatric illnesses. It covers all categories of mental health disorders for both adults and children, with a current listing of 297 disorders. Importantly, one of the major revisions made from the DSM-IV to the DSM-5 was the classification of mild and major neurocognitive disorders. Dementia, for example, is now defined as a major neurocognitive disorder.

In the News

Damage control. The harmful health consequences of smoking and drinking alcohol are no secret. But, with the use of MRI, researchers can now show that these vices cause premature aging of the brain—even in people with no cognitive impairment. Using structural MRI data from over 12,000 people without cognitive impairment from the UK Biobank, researchers found statistically significant differences in the relative brain ages of heavy smokers and drinkers vs those who did not smoke or drink alcohol. For example, smoking a pack of cigarettes every day for 1 year was associated with 0.03 years of increased relative brain age (a measure of whether their brains experienced faster or slower aging compared with their peers). And the effects of drinking alcohol every day or on most days was similar. For each additional gram of alcohol consumed per day, researchers saw a 0.02-year increase in relative brain age. Yet another reason to help patients get a handle on these bad habits and quit while they’re ahead (pun intended!).

The knee bone’s connected to the…head bone? Adding to the news about the body-brain connection, researchers have found that patients who undergo anterior cruciate ligament (ACL) reconstruction may also experience structural changes to their brains. To determine the link between excitability and corticospinal tract structure in patients with ACL reconstruction, the researchers performed MRI brain scans on 10 patients who underwent this procedure. They found evidence of atrophy in patients’ corticospinal tracts. Specifically, the side of the corticospinal tract that controlled the ACL-reconstructed was about 15% smaller than the tract on the uninjured side. This narrowing means that less information can travel from the brain to the muscles in the knee. The researchers postulated that these changes may be a sort of protective mechanism put in place by the body to limit unwanted movement around an injured joint, adding that this may also occur with other musculoskeletal injuries. Based on their findings, the researchers suggested that a systemic approach to rehabilitation in these patients may be better. They also noted that, rather than focusing only on improving range of motion or alleviating joint swelling, using biofeedback and other visual training modalities could help rewire the brain to facilitate injury recovery. Pretty convincing, no?

This cardinal migraine symptom is the most common. The cardinal-associated symptoms of migraine are nausea, phonophobia, and photophobia. But, which of these symptoms is most common and most bothersome among migraineurs? To find out, researchers analyzed 6-month follow-up survey data from the Migraine in America Symptoms and Treatment (MAST) study. Eligible survey respondents (n = 6,045; mean age: 47 years) included those who reported ≥ 3 monthly headache days (MHDs) in the past 3 months and at least 1 MHD in the past 30 days.

In all, 64.9% of respondents reported experiencing all three cardinal migraine symptoms. However, 49.1% reported photophobia to be their most bothersome symptom (MBS), while 28.1% and 22.8% reported nausea and phonophobia, respectively. Interestingly, those who reported photophobia as their MBS were more likely to be men, obese, and have visual aura. Those in whom nausea was the MBS were more likely to be women, have lower income, and lower levels of treatment optimization. Finally, those in whom phonophobia was the MBS were more likely to have cutaneous allodynia and less likely to have visual aura. So, photophobia is the most common MBS, something to keep in mind when treating your patients with migraine.

Neuro Trivia

How many brain-imaging techniques can you name?

There are 15 brain-imaging techniques: magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), magnetic resonance spectroscopy, positron emission tomography (PET), optical intrinsic signal (OIS), computed axial tomography (CT), diffuse optical imaging (DOI), event-related optical signal (EROS), electroencephalography (EEG), magnetoencephalography (MEG), single photon emission computed tomography (SPECT), single-photon emission computed tomography, cranial ultrasound, and near infrared spectroscopy (NIS).

Novel Diagnostics

Easier Dx of cerebral small vessel disease. Significantly higher levels of six blood proteins may be indicative of increased cerebral small vessel disease (CSVD) risk, according to new research. CSVD affects an estimated 11 million older US adults and can lead to dementia and stroke. About 25% of all strokes in the United States are associated with CSVD. Because CSVD can only be diagnosed via MRI brain scans, many cases go undiagnosed due to mild symptoms often attributed to normal aging, such as troubles with memory or walking. But, researchers have just found that six serum proteins may be the key to early CSVD diagnosis.

In their study, researchers assessed the levels of these six blood proteins as well as MRI and diffusion tensor imaging scans from patients (mean age: 76.4 years) with normal cognition or only mild cognitive impairment. Patients who showed signs of CSVD upon imaging had significantly higher levels of the six serum proteins. Those with higher-than-average levels were also twice as likely to have CSVD on MRI and were 10% more likely to have early signs of white matter damage. Furthermore, for every CSVD risk factor participants had—including high blood pressure, diabetes, or previous stroke—levels of these proteins doubled. The researchers validated their findings by performing blood tests in a group of participants at much higher CSVD risk. They are hopeful that their results will lead to the development of a blood test to diagnose CSVD.

MRI discrimination. The use of high-resolution MRI to detect nigrosome-1 may help clinicians distinguish Parkinson disease (PD) from essential tremor, according to a new study. The nigrosome-1 area is in the caudo-lateral region of the pars compacta, within the substantia nigra. It is comprised of a significant number of dopaminergic neurons and, in early PD, degenerates. For this case-control study that included 16 patients with PD and 16 with essential tremor, researchers performed MRI studies with a 3T MRI scanner, with a susceptibility weighted imaging sequence (axial plane; isotropic voxel: 0.75 mm). All studies were assessed by two evaluators. The first evaluator reported an absence of the nigrosome-1 area in 15 patients with PD and in 2 with essential tremor. The second evaluator noted an absence of the nigrosome-1 area in 15 patients with PD patients and in 4 with essential tremor. Thus, for diagnosing PD, the sensitivity of nigrosome-1 was 93.75% and the specificity was 87.5% for the first evaluator. For the second evaluator, these rates were 93.75% and 75%, respectively. Moral of the story: imaging to detect the nigrosome-1 area may be your friend in distinguishing PD from essential tremor.

Novel Treatments

A better approach to spinal injections? An international team of researchers—led by scientists at the University of California San Diego School of Medicine (UCSD)—may have found a new, less invasive injection technique that could boost spinal cord injury repair. Current spinal cell delivery modes, which involve the direct injection of cells into the spinal parenchyma, run the risk of further damaging spinal tissue or causing intraparenchymal bleeding. The researchers’ novel delivery method involves the deposit of neural precursor cells (NSCs) into the spinal subpial space instead. NSCs are stem cells that can differentiate into various types of neural cells, depending on where they are. As such, they offer great promise in treating many neurodegenerative diseases as well as spinal cord injuries. This minimally invasive technique reduces the risk of further injury while promoting the spread of reparative cells. Plus, it allows for the delivery of a high number of cells in a single injection. The injected cells then take on the properties of the surrounding cells. Researchers are hopeful that subpial injection will—in the future—have applications for other spinal neurodegenerative disorders, including spinal traumatic injury, amyotrophic lateral sclerosis, and multiple sclerosis. The new technique is currently in preclinical trials, but researchers are hard at work finding optimal dosing and timing.

Old dog, new trick. Granulocyte-colony-stimulating factor (GCSF) is currently used to treat chemotherapy-induced neutropenia. It is also used to stimulate blood cell formation in patients who need bone marrow transplants. But, researchers of a new studysuggest that GCSF may also offer neuroprotection against autophagy and mitochondrial stress in vivo. As such, the drug may have potential in the treatment of stroke. Their results support the hypothesis that GCSF is one of the only growth factors that may reduce infarction by decreasing stress on the endoplasmic reticulum and mitochondria. In a murine model, researchers assessed the pro-survival mechanisms of GCSF against autophagy-induced apoptosis, mitochondrial stress, and endoplasmic reticulum stress. Proof of the neuroprotective benefit of GCSF gene therapy in a mouse stroke model came in the form of a decrease in dynamin-related protein—a marker of mitochondrial stress—in the frontal and middle brain. These researchers have been developing GCSF as a therapeutic method to replenish new brain cells due to its ability to preserve the CNS, suppress apoptosis, and elicit both neurogenesis and angiogenesis. And, its potential neuroprotection could extend to other neurological diseases, such as Parkinson disease. Talk about great multitasking potential!

A different approach to Alzheimer disease. Researchers have identified a new compound that may have clinical utility in the treatment of Alzheimer disease. The novel compound, C1, works to inhibit amyloid production and thus reduce fibril formation in the brains of patients with Alzheimer disease. Specifically, C1 is a covalent gamma-secretase inhibitor that prevents the enzyme gamma-secretase from producing amyloids. This differs from what traditional enzyme inhibitors do (ie, block the active site on gamma-secretase). C1 binds to the cleavage site of the precursor protein instead of directly to gamma-secretase. By doing so, C1 may circumvent the typical severe side effects of traditional enzyme inhibitors, which stop all normal function of this enzyme. A new blocker for amyloid production? Their research is patent pending.

New in Patient Management

Pass the dark leafy greens, please! Elderly individuals who consume a flavonol-rich diet may be less likely to develop Alzheimer disease. Flavonols, phytochemicals found in plant pigments, are known to have antioxidant and anti-inflammatory properties. In a recent study, researchers focused on four flavonols in particular: kaempferol (found in kale, beans, tea, spinach, and broccoli), quercetin (found in tomatoes, kale, apples, and tea), myricetin (found in tea, wine, kale, oranges, and tomatoes), and isorhamnetin (found in pears, olive oil, wine, and tomato sauce). After following 921 people (aged 81 years at baseline) without dementia for approximately 6 years, the researchers found that those who consumed the most flavonols (about 15.3 mg/d) were 48% less likely to develop AD compared with those who ate the least (about 5.3 mg/d). Furthermore, participants who had the highest intake of either isorhamnetin or myricetin had a 38% lower risk of AD, while those with the highest consumption of kaempferol had a 51% lower risk. Interestingly, quercetin intake was not associated with AD risk. Just more data showing that a healthy and diverse diet can make a difference to brain health! Mangia!

BP is important. Targeting mean arterial blood pressure (MABP) after endovascular therapy for acute ischemic stroke may help you reduce poor functional outcomes in these patients. In a recent analysis of datasets from three randomized clinical trials—SIESTA, ANSTROKE, and GOLIATH—researchers found that patients with prolonged low or high MABPs had worse neurologic outcomes. This finding validates that the traditional U-shaped association between BP and outcome in patients with ischemic stroke extends to an association between BP changes during endovascular therapy and functional outcomes. The researchers also found that the critical thresholds for poor outcome were an MABP of less than 70 mmHg for more than 10 minutes and an MABP greater than 90 mmHg for more than 45 minutes. So, keep close tabs on those BPs. It’s a simple, easy way to assure good outcomes in your patients after endovascular therapy.

Easier prognosticating. Bell palsy—also known as idiopathic facial paralysis—is the most common cause of unilateral facial paralysis. Although this condition is most commonly treated with corticosteroids and antiviral agents, there are no clear guidelines outlining treatment, and knowledge on prognosis following treatment is limited. To determine factors associated with better outcome in these patients, researchers from South Korea studied 1,364 patients (mean age: 47 years; > 50% female) with primary Bell palsy who had been treated at an outpatient clinic. Patients received either oral corticosteroids (oral prednisolone tapered over 10 days) or corticosteroids plus antiviral agent (oral acyclovir or famciclovir for 5 to 7 days) within 1 week of onset of their paralysis. Favorable outcomes—defined as House-Brackmann grade I or II at 6-month follow-up—were seen in 80.6% of patients. Researchers found that younger age, a lower degree of initial facial nerve paralysis, an absence of pathological spontaneous fibrillation activity, no diabetes, and well-managed hypertension were all factors associated with favorable outcomes. Assessing these factors in your patients with Bell palsy may help you to better identify which are more likely to have a better prognosis.

‘Script control. Because dementia is often accompanied by comorbidities managed with multiple medications, there is a high risk for potentially inappropriate prescribing and, consequently, adverse drug reactions. In a recent review, researchers found that the prevalence of potentially inappropriate prescribing in patients living with dementia ranged from 14% to 64%. In the community, the prevalence was 31%, while in nursing/care homes, it was 42%. Potentially inappropriate prescribing included prescribing likely related to dementia (eg, hypnotics, sedatives, cholinesterase inhibitors, antipsychotics, etc.) and prescribing related to the treatment of comorbidities (eg, cardiovascular drugs, non-steroidal anti-inflammatories, antacids, etc). They found that high comorbidity levels were associated with an increased risk of potentially inappropriate prescribing. Food for thought when prescribing for your elderly dementia patients.

Latest in Peer-Reviewed Studies

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Upcoming Medical Meetings

53rd Annual Recent Advances in Neurology, in San Francisco, CA, February 12-13, 2020

American Society of Spine Radiology (ASSR) 2020 Annual Symposium, in Dana Point, CA, February 12-16, 2020

International Stroke Conference 2020, in Los Angeles, CA, February 18-21, 2020

North American Spine Society’s (NASS) Evidence & Technology Spine Summit, in Park City, UT, February 19-22, 2020

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