Is the bleeding risk of thrombolysis increased in those on dual antiplatelets?

Safety and efficacy of dual antiplatelet pretreatment in patients with ischemic stroke treated with IV thrombolysis: a systematic review and meta-analysis. Malhotra K, Katsanos AH, Goyal N, et al. Neurology 2020; 94:e657-e666. Abstract OBJECTIVE: Conflicting data exist on the safety and efficacy of IV thrombolysis (IVT) in patients with acute ischemic stroke (AIS) receiving dual […]

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Meet Pete

This is Peter Mellett Pete lives in Wadebridge, a picturesque town tucked nicely in the Cornish countryside. *** Pete loves going on cycling trips. But above every thing else, he loves reading his two adorable children to sleep. *** But for us at Neurochecklists… Pete is a genius at web development. He has taken the […]

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The case for testing serum neurofilament light protein in MS

I am yet to request serum neurofilament light protein (NfL) in my practice. I am not sure yet why I should, but until now I confess I really haven’t looked for a reason to do so. I however know that some MSologists now tick it, along with other blood tests, when they investigate people they suspect may have multiple sclerosis (MS). NfL are proteins that are released by damaged neurones. Should I be requesting NfL in my clinical practice? I sniffed around to find the case for testing serum NfL, and below is what I found.

By GerryShaw – Standard tissue culture and immunofluorescencePreviously published: Unpublished, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=26518273

Many studies have looked at the value of NfL in MS. One such very well-planned study that addresses many of my questions is that by Guili Disanto and colleagues, published in the journal Annals of Neurology in 2017. In the paper, titled Serum Neurofilament light: a biomarker of neuronal damage in multiple sclerosis, the authors studied >380 people with MS and >150 healthy controls, and report four important findings.

By GerryShaw – Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=17500647
  1. The levels of NfL in serum strongly correlate with the levels in cerebrospinal fluid (CSF) of people with MS.
  2. People with more active and more severe MS had higher levels of NfL.
  3. People with MS on disease modifying treatment (DMT) had lower NfL levels than those who were not on treatment.
  4. In people with MS who had their serum NfL tested serially over time, the level of NfL predicted those who will develop frequent relapses or progressive MS.

The authors concluded, with enough justification I think, that serum NfL is a “sensitive and clinically meaningful blood biomarker to monitor tissue damage and the effects of therapies in MS“.

Culture rat hippocampal neuron. ZEISS Microscopy on Flickr. https://www.flickr.com/photos/zeissmicro/24327909026

The strong correlation between cerebrospinal fluid (CSF) and serum NfL was also confirmed by a study published in the journal Neurology, by Lenka Novakova and colleagues titled Monitoring disease activity in multiple sclerosis using serum neurofilament light protein. As the title indicates, they discovered that serum NfL is as good as CSF NfL in monitoring the progression of MS.

Neuron. NICHD on Flickr. https://www.flickr.com/photos/nichd/21086076575

The observation that NfL predicts the course of MS is supported by many other studies, such as the one by Kristin Varhaug and colleagues in the journal Neurology Neuroimmunology and  Neuroinflammation whose title is also self-explanatory: Neurofilament light chain predicts disease activity in relapsing-remitting MS. A more recent paper, also published in Neurology, further reinforces the benefit of serum NfL in disease course prediction. It is titled Blood neurofilament light chain as a biomarker of MS disease activity and treatment response. In this paper, Jehns Kuhle and colleagues practically confirm all the above stated benefits of NfL, concluding that “our results support the utility of blood NfL as an easily accessible biomarker of disease evolution and treatment response”.

“Neuron” by Roxy Paine. Christopher Neugebauer on Flickr. https://www.flickr.com/photos/chrisjrn/4745660322

As for long term outcome, the 10 year follow up study by Alok Bahn and colleagues, published in the Multiple Sclerosis Journal in 2018, is most informative. In their paper titled Neurofilaments and 10-year follow-up in multiple sclerosis, the authors noted that “CSF levels of NfL at the time of diagnosis seems to be an early predictive biomarker of long-term clinical outcome and conversion from RRMS to SPMS”. Further support for the long term prognostic value of serum NfL comes from a paper published in 2018 in the journal Brain titled Serum neurofilament as a predictor of disease worsening and brain and spinal cord atrophy in multiple sclerosis. The authors, Christian Barro and colleagues, studied more than 250 people with MS and concluded that “the higher the serum neurofilament light chain percentile level, the more pronounced was future brain and cervical spinal volume loss“.

Nervous Tissue: Spinal Cord Motor Neuron. Berkshire Community College on Flickr. https://www.flickr.com/photos/146824358@N03/41850849912/in/album-72157666241437517/

It is pertinent to note that the MS sphere is not the only one in which NfL is making waves. It has been found to be elevated in many other disorders such as motor neurone disease (MND), multiple system atrophy (MSA), hereditary spastic paraplegia (HSP), stroke, active small vessel disease, and peripheral neuropathy (PN). With these disclaimers in place, it may just be time to start ticking that NfL box.

 

By GerryShaw – Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=17502311

 

Does adolescent concussion predispose to multiple sclerosis?

Concussion in adolescence and the risk of multiple sclerosis: a retrospective cohort study. Povolo CA, Reid JN, Shariff SZ, Welk B, Morrow SA. Mult Scler 2020 (Epub ahead of print). Abstract BACKGROUND: Physical trauma, specifically concussions sustained during adolescence, has been hypothesized to be a risk factor for multiple sclerosis (MS). OBJECTIVE: To examine the association between adolescent concussions and future MS diagnosis. METHODS: This retrospective study using […]

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COVID-19 checklists: revised and updated

This is just a short blog post to let you know that… As promised, we have updated and revised our: Coronavirus COVID-19 Checklists As always, They remain concise and practical And of course fully referenced And as new data emerges We shall continue to update our checklists

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Is thrombolysis effective in spinal stroke?

Acute ischemic myelopathy treated with intravenous thrombolysis: four new cases and literature review. Jankovic J, Rey Bataillard V, Mercier N, Bonvin C, Michel P. Int J Stroke 2019; 14:893-897. Abstract BACKGROUND: Intravenous thrombolysis is a well-established treatment of ischemic stroke within 4.5 h. However, its effectiveness in acute ischemic myelopathy is unknown. PURPOSE: We describe a […]

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Is blood monitoring useful for patients on IVIg therapy?

Routine blood monitoring in maintenance immunoglobulin treatment of inflammatory neuropathy: Is it clinically relevant? Keh R, Kahlil A, Nihoyannopoulos L, et al. J Neurol Sci 2020; 408:116527. Abstract BACKGROUND: Pre-treatment screening for IgA deficiency and close monitoring of full blood count(FBC) and renal function is recommended with intravenous immunoglobulin(IVIg) therapy in neurological diseases. AIMS: To […]

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What features predict poor outcome following shunt surgery for NPH?

Negative predictors of shunt surgery outcome in normal pressure hydrocephalus. Bådagård H, Braun M, Nilsson D, Stridh L, Virhammar J. Acta Neurol Scand 2020; 141:219-225. Abstract OBJECTIVES: The prevalence of idiopathic normal pressure hydrocephalus (iNPH) and vascular comorbidity increases with age. It has not been clarified if high age and vascular disease are negative predictors of […]

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The cutting-edge applications of ultrasound in neurology

Imaging is central to neurological practice. It doesn’t take much to tempt a neurologist to ‘order’ or ‘request’ an MRI or a CT. In appropriate circumstances the imaging is a DAT scan, and with a bit more savvy, exciting imaging modalities such as amyloid scans and tau PET scans. In the playpen of the neurologist, the more ‘high tech’ the imaging technology, the more cutting-edge it feels-even if it doesn’t make much of a difference to the patient. Ultrasound on the other hand is the mongrel of imaging technologies. Too simple, too cheap, too available, too unsophisticated-not better than good old X-rays. It is safe to assume that the pen of the neurologist hardly ever ticks the ultrasound box. What for?
prd brain scan. Patrick Denker on Flickr. https://www.flickr.com/photos/pdenker/74684051
And yet, ultrasound has an established, even if poorly appreciated, place in neurological imaging. It is perhaps best known for its usefulness in assessing carpal tunnel syndrome at the wrist. But, for the neurologist, CTS is sorted out by wrist splints, steroid injections, and decompression surgery-forgetting that there may just be a ganglion, a cyst, or a lipoma lurking in there. Ultrasound also has a place in the assessment of muscle disorders, picking up anomalies and detecting distinctive muscle disease patterns. The only problem is that, even when radiologists and neurologists put their heads together, they struggle to understand what the patterns actually mean. And since the first pass of this blog post, I was reminded of the place of ultrasound-guided lumbar puncture in improving the safety and accuracy of this otherwise blind procedure. And there are even guidelines to help takers. My guess is that most neurologists prefer the thrill of hit-and-miss that goes with conventional LP. For many reasons therefore, the ultrasound box remains un-ticked.
By RSatUSZ – PACS UniversitätsSpitalZürich, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=11272585
Despite these limitations, the place of ultrasound remains entrenched in neurological practice. Indeed, ultrasound has been spreading its wings to exotic places, broadening its range, and asserting its presence. Perhaps it is time to reconsider the humble ultrasound, and to catch up with what it has been up to. Here then are 3 emerging roles of ultrasound in neurology

Therapeutic ultrasound

The role of ultrasound in treatment is reviewed in the excellent paper in Nature Neurology titled Ultrasound treatment of neurological diseases-current and emerging applications. And the emphasis is on trans-cranial MR-guided focused ultrasound (tcMRgFUS). tcMRgFUS is making waves in the treatment of essential tremor (ET), Parkinson’s disease (PD), and central pain. The benefit for PD is already filtering out into the popular press such as this article in STAT titled New treatment offers some hope for an unshakable tremorUltrasound is also rapidly emerging as an option in the ablation of brain tumours, and in the treatment of stroke (sonothrombolysis). 

By Images are generated by Life Science Databases(LSDB). – from Anatomography, website maintained by Life Science Databases(LSDB).You can get this image through URL below. https://commons.wikimedia.org/w/index.php?curid=7845026

Drug delivery into the brain

The blood brain barrier is a rigidly selective barricade against most things that venture to approach the brain-even if their intentions are noble. This is a huge impediment to getting drugs to reach the brain where they are badly needed. It is therefore humbling that it is the simple ultrasound that is promising to smuggle benevolent drugs across the blockade to aid afflicted brains. This was reported in the journal Science Translational Medicine, and the article is titled Clinical trial of blood-brain barrier disruption by pulsed ultrasound. The trial subjects were people with the notorious brain tumour, glioblastoma. They were injected with their conventional chemotherapy drugs, delivered along with microbubbles. The blood brain barrier was then repeatedly ‘pelted’ with pulsed ultrasound waves; this seem to leapfrog the drugs into the brain in greater than usual concentrations, enough to do a much better job. This surely makes films such as Fantastic Voyage and Inner Space not far-off pipe-dreams.

Bubbles. Jeff Kubina on Flickr. https://www.flickr.com/photos/kubina/153871892

Treatment of coma

Some of the emerging neurological applications of ultrasound are even more Sci-Fi than pulsed ultrasound. And a sign of this Sci-Neuro world is this report titled UCLA scientists use ultrasound to jump-start a man’s brain after coma. One is tempted to dismiss this as ‘fake news’ but it is a proper case report, in a proper scientific journal, Brain Stimulation, and with a proper scientific title, Non-Invasive Ultrasonic Thalamic Stimulation in Disorders of Consciousness after Severe Brain Injury: A First-in-Man Report. By targeting ultrasounds to the subject’s thalamus, the authors assert, the subject just woke up (and presumably asked for a hot cup of tea!). A word of caution is however needed; the authors rightly point out that it may have all been…coincidental!

The awakening (arm). Jeff Kubina on Flickr. https://www.flickr.com/photos/kubina/153871892

Ultrasound is clearly humble no more.

Big ambition trumps humble beginnings.

Do seizures at stroke onset increase the risks of thrombolysis?

TRISP Collaborators. Intravenous thrombolysis for suspected ischemic stroke with seizure at onset. Polymeris AA, Curtze S, Erdur H, et al; TRISP collaborators Ann Neurol 2019; 86:770-779. Abstract OBJECTIVE: Seizure at onset (SaO) has been considered a relative contraindication for intravenous thrombolysis (IVT) in patients with acute ischemic stroke, although this appraisal is not evidence based. Here, we investigated the prognostic significance of SaO […]

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