Cerebrovascular disease in patients with COVID-19: neuroimaging, histological and clinical description. Hernández-Fernández F, Valencia HS, Barbella-Aponte RA, et al. Brain 2020 (Online ahead of print). Abstract Background: Since the appearance of the first case of coronavirus disease 2019 (COVID-19) a pandemic has emerged affecting millions of people worldwide. Although the main clinical manifestations are respiratory, […]What are the characteristics of stroke in COVID-19? — Neurochecklists Blog
Guillain-Barré syndrome spectrum associated with COVID-19: an up-to-date systematic review of 73 cases. Abu-Rumeileh S, Abdelhak A, Foschi M, Tumani H, Otto M. J Neurol 2020 (Online ahead of print). Abstract Background: Since coronavirus disease-2019 (COVID-19) outbreak in January 2020, several pieces of evidence suggested an association between the spectrum of Guillain-Barré syndrome (GBS) and […]What is the picture of Guillain Barre syndrome in COVID-19? — Neurochecklists Blog
In our continuing zeal to maintain a grip on all of neurology, We regularly add to our already exhaustive database of checklists. As a taster of what we have recently done, Below are 15 brand new checklists expanding our horizon. *** Acute amnestic syndromes Alzheimer’s disease preventative measures Antiplatelet resistance: causes Antiplatelet resistance: management Encephalocraniocutaneous […]A few more helpful and practical neurology checklists — Neurochecklists Blog
It is difficult to really say when neuroscience began, but most sources trace the first account of the nervous system to what is now known as the Edwin Smith papyrus; this is an Egyptian text written around 1700 B.C which documents surgical procedures for brain trauma. Since then, neuroscience breakthroughs have come at breakneck speed. The sources I have consulted for this blog post, referenced at the end, name innumerable discoveries made by countless innovators. To attempt to put a number to the most important breakthroughs will therefore be a well-nigh impossible task. So I came up with the idea of chunking key discoveries under distinct sections or systems of the nervous system.
But even this plan to chunk key breakthroughs came with strong challenges. For example, it is not always clear when a discovery was first made, or who crossed the finishing line first. This is because there are often several contenders in a tight race to the finish, and only a few discoveries were definite one-man paradigm-changing works. On the contrary, most discoveries were made by two or three pioneers working in a creative partnership, or by larger groups of people working in innovative collaborations. A further challenge was establishing what or where the finishing line was, as this is not always well-defined; this is understandable because most scientific advances were made over centuries, in small incremental steps, in a gradual progression from basic observation to complex synthesis.
To overcome these challenges, I have avoided too much emphasis on the ‘who first‘ conundrum that drives, and sometimes mires, science. I have also side-stepped the ‘when first‘ problem by noting only a few dates just to maintain some sense of chronology. I did a lot of picking and choosing for this post, and it is inevitable that somebody’s favourite discovery, or discoverer, would be missing; take heart and exult in the collective effort that has gone into these monumental breakthroughs in the history of neuroscience.
Cerebrospinal fluid (CSF)
It is difficult to pinpoint who first described the cerebrospinal fluid (CSF) circulation but Nicolo Massa, Lewis Weed, Gustav Retzius, Francois Magendie and Albrecht von Haller have all been cited. The names associated with accurately describing the constituents of CSF are William Halliburton and William Mestrezat. Franciscus de la Boe Sylvius is credited with describing the aqueduct of Sylvius, and Alexander Monro for describing the foramen of Monro. Antonio Pacchioni discovered arachnoid granulations, whilst Guilio Cesare and Thomas Willis are credited for describing the anatomy and function of the choroid plexus. The accurate description of the blood brain barrier has been attributed to both Max Lewandowsky and Paul Erlich.
Cerebral localisation of functions has always been, and continues to be, a key neuroscience task. As brain functions become increasingly recognised as network-based, rather than region-based, cerebral localisation is taking more of a back seat in neuroscience. But it is still worthwhile to acknowledge the pioneers who identified key brain areas. Paul Broca is credited with the first description of the cortical speech area, whilst motor function localisation is traced to the works of Eduard Hitzig, Gustav Fritsch, David Ferrier, and Victor Horsley. The classification of cerebral areas into 52 parts was done by Korbinian Brodmann, whilst it was neurosurgeon Wilder Penfield who defined the cortical maps of the motor and sensory homunculus.
Both Rudolph Virchow and Heinrich Müller are credited with describing neuroglia. The credit for classifying these into microglia and oligodendroglia goes to Pio del Rio Hortega, whilst that for describing dendrites and axons goes to Otto Friedrich Karl Deiters. Camillo Golgi introduced the critical silver nitrate method of staining nerve cells, a technique advanced by Santiago Ramon y Cajal, who developed the gold chloride-mercury method for staining astrocytes. The description of the synapse is attributed to the truly great Charles Scott Sherrington. W. Bevan Lewis, Vladimir Betz and Johannes Purkinje have all been credited with describing the giant motor nerves of the cortex.
Rufus of Ephesus is named as the first person to describe and name the optic chiasma. Other cranial nerve achievements are the discovery of the tenth cranial nerve by Marinus, and the description of seven cranial nerves by Rhazes. The trochlear and abducens nerves were described by Gabriele Falloppio, and it was Samuel Thomas von Soemmerring who introduced the current classification of the twelve cranial nerves.
The credit for distinguishing between myelinated and unmyelinated nerves goes to Robert Remak, whilst the credit for describing myelin formation goes to Theordor Schwann. It was Louis-Antoine Ranvier who described the gaps between myelin sheaths called the nodes of Ranvier. The different types of sensory nerves were described by Herbert Gasser, and it was Friedreich Merkel who described the sensory receptors now known as Merkel corpuscles. Credit for describing the cutaneous distribution of sensory nerves goes to Henry Head, and it was Francois Magendie who recognised the different functions subserved by the dorsal and ventral nerve roots of the spinal cord.
The early understanding of how nerves function has a lot to do with the description by Hermann Helmholtz of the electrical nerve impulse velocity. The resting membrane potential was described by Julius Bernstein and Walter Nernst, whilst Keith Lucas and Edgar Adrian measured peripheral nerve impulses, Adrian going on to confirm that nerve impulses are all or none. Alan Hodgkin and Andrew Huxley are credited with describing the mechanisms of action potentials, whilst Joseph Erlanger and Herbert Spencer Gasser described the function of single nerve fibers.
Whilst nerve function is electrical, it is chemicals that bridge the gap between nerves. The chemical neurotransmitters of peripheral nerves, norepinephrine and acetylcholine, were isolated by George Barger and Henry Dale. The credit for establishing chemical neurotransmission between nerves and muscles, at the neuromuscular junction, goes to Otto Loewi‘s dream-inspired work on Vagusstoff. The discovery of the central nervous system neurotransmitter GABA is credited to Eugene Roberts and Jorge Awapara. Most of the later work on neurotransmitters were made by Julius Axelrod, Bernard Katz and Ulf Svante von Euler, and the credit for elucidating the function of ion channels goes to Erwin Neher and Bert Sakmann.
The visual system is fundamental to neuroscience, and credit for describing its mechanism goes to Ragnar Granit, Halden Hartline and George Wald. The merit for elucidating the details of visual processing goes to David Hubel and Torsten Wiesel. The sense of smell is similarly important, and initial work on this was made by David Ferrier, but it is to Linda Buck and Richard Axel that kudos go for discovering odour receptors, and for describing the configuration of the olfactory system.
Memory, pain, and prions
The acclaim for establishing the anatomical foundations of memory goes to Brenda Milner for her work on Patient HM. It is however Eric Kandel who has the honour of working out the functional process of memory formation. The gate control theory of pain was established by Ronald Melzack and Patrick Wall, whilst credits for establishing the nature of prion diseases go to the lively Daniel Carleton Gajdusek, and the indefatigable Stanley Prussiner.
Navigation, mirror neurones, and growth factors
The brain’s positioning system was discovered by John O’Keefe, Edvard Moser, and May-Britt Moser. Cedit for discovering mirror neurones goes to Giacomo Rizzolatti, whilst Rita Levi-Montalcini and Stanley Cohen were the first to isolate nerve growth factor.
Brain circulation and brain waves
Thomas Willis, Henry Duret and Johann Heubner first described the arterial circulation of the brain, whilst the electrical brain wave activity of the brain was first recorded by Hans Berger, incidentally when he was investigating telepathy.
And so ends this rapid whizz through the annals of neuroscience. This is just the condensed tip of the iceberg; to learn more about the fascinating giants who defined the glorious history of neuroscience, you may wish to slowly digest the following sources:
As the dust clears, and the froth settles, the picture of how COVID 19 impacts the nervous system is taking form. As eager neuroscientists track down case reports and carry out surveys, gently winnowing out the chaff from the wheat, a clearer picture is beginning to emerge. As the neurological cartographers map the path of […]15 things we now know about COVID19 and the nervous system — Neurochecklists Blog
Descartes’ Error Author: Antonio Damasio Synopsis The main assertion made by this groundbreaking book on human emotions is simply that our feelings are right at the centre of ‘the loop of reason‘, playing a positively influential role in decision-making and social behaviour (page xvi-xvii). The book’s main argument is that emotions are indispensable for making good […]
Like something from a futuristic medical thriller, you have mice diagnosing bladder tumours, and dogs detecting prostate cancer, just by sniffing the urine of patients. And like a plot from a Sci-Fi film, dogs are also trained to smell-out malaria. But we are not forward to the future – we are still in the here and now. And it is not just cats, dogs, and mice; pouched rats and nematodes have staked their claim as well. And the number of diseases that pets can presumably detect grows longer by the day (OK perhaps by the year), and these range from diabetic hypoglycaemia, colorectal cancer and migraine, to infections such as Clostridium difficile and tuberculosis. And whilst there are many animals in on the act, they are just bit players on this set – dogs are by far the superstars of the show.
As weird as it may sound, many of the reports being anecdotal, there are actually grains of truth and crumbs of evidence supporting the claim that pets are not just for Christmas. For example, there is a trail of research studies confirming the effectiveness of seizure detecting dogs; one paper specifically reports that they enabled 90% of subjects to reduce their seizure frequency by 34-50%. Although the time from seizure-detection to the actually seizure varies wildly, from 10 seconds to 5 hours before the epileptic attack, there seems to be enough time in most cases for the subject to take preventative measures.
But not all dogs are as skilled in the act as others, and your best bet is on alerting dogs which have a stronger bond with their owners. And if you want to pick a dog for its seizure-detecting skills, go for one that scores high in motivation…and low in neuroticism. This is important because the ability of dogs to detect seizures is not always benign; they are known to respond by attacking the subject or their helpers as part of an untrained fight or flight reaction. It is important therefore that seizure-alerting dogs are trained not to be stressed, and to respond appropriately.
But what are dogs actually detecting when they detect seizures? The conventional theory is that they are responding to subtle changes in behaviour; this may therefore explain why dogs can also warn of impending non-epileptic attacks, an observation that has been duplicated in another paper. The other possibility however is that the dogs are detecting disease-specific odours. This concept should not be surprising because, for example with infections, it has been shown that endotoxins induce a detectable aversive body odour. Similarly with liver disease, exhaled breath is already being considered in sorting out differential diagnoses. One premise behind the disease-odour hypothesis is the existence of disease-specific volatile organic compounds (VOCs). It feels all so exciting-no wonder there is now a well-developed scientific field of exhaled air analytics.
But as with all things in life, and particularly in science, here are always the naysayers, the gatecrashers to the party. And so it is that, with the case of seizures, there are those who are not convinced that pets possess the guile to pick up seizures. For example, in a small study of 3 subjects in an epilepsy monitoring unit, Rafael Ortiz and Joyce Liporace, reporting in the journal Epilepsy and Behaviour, found that seizure alert dogs were not effective in predicting seizures. In another paper published in the journal Epilepsy Research, titled Can seizure-alert dogs predict seizures?, Stephen Brown and Laura Goldstein observed that there is “no rigorous data” to support the assertion that seizure alert dogs accurately predict seizures. Another detailed review in Plos One in 2018, by Amélie Catala and colleagues, concluded that appropriate empirical evidence that dogs can alert or respond to epileptic seizures is still missing.
But as the overused cliché goes, absence of evidence is not the evidence of absence. So how can we prove that dogs are indeed detecting seizure-specific odours? This is the task Amélie Catala and her colleagues also set out to accomplish when they made 5 dogs to sniff the odours obtained from 5 people with epilepsy. They tasked the dogs to tell apart the odours obtained around the time of the subjects’ seizures, from the odours obtained at other times when there were no proximate seizures. Reporting their findings in Science Report in 2019, under the title Dogs demonstrate the existence of an epileptic seizure odour in humans, they found that all the 5 dogs easily distinguished the seizure-related odours from the non-seizure related odours. But the small scale of the trial (were there just not enough dogs to go round?) justifies the authors’ call for larger trials to confirm their findings.
This is clearly still a grey area in epilepsy management, but one with a high potential if explored further. Are there any pet-loving neurologists willing to get in on the act? Do come along with your pets!
Complete Epstein-Barr virus seropositivity in a large cohort of patients with early multiple sclerosis. Abrahamyan S, Eberspächer B, Hoshi MM, et al. JNNP 2020 (Online ahead of print). Abstract Objective To determine the prevalence of antibodies to Epstein-Barr virus (EBV) in a large cohort of patients with early multiple sclerosis (MS). Methods Serum samples were […]
The Emotional Brain Author: Joseph LeDoux Synopsis What are emotions, and how are they made? These are the main questions this book, written by one of the foremost researchers in the field, sets out to answer. Acknowledging that the ‘amazing and perplexing’ nature of emotions makes it difficult for scientists to agree on a definition […]
Medicine is as much defined by diseases as by the people who named them. Neurology particularly has a proud history of eponymous disorders which I discussed in my other neurology blog, Neurochecklists Updates, with the title 45 neurological disorders with unusual EPONYMS in neurochecklists. In many cases, it is a no brainer that Benjamin Duchenne described Duchenne muscular dystrophy, Charle’s Bell is linked to Bell’s palsy, Guido Werdnig and Johann Hoffmann have Werdnig-Hoffmann disease named after them. Similarly, Sergei Korsakoff described Korsakoff’s psychosis, Adolf Wellenberg defined Wellenberg’s syndrome, and it is Augusta Dejerine Klumpke who discerned Klumpke’s paralysis. The same applies to neurological clinical signs, with Moritz Romberg and Romberg’s sign, Henreich Rinne and Rinne’s test, Jules Babinski and Babinski sign, and Joseph Brudzinski with Brudzinki’s sign.
Yes, it could become rather tiresome. But not when it comes to diseases which, for some reason, never had any names attached to them. Whilst we can celebrate Huntington, Alzheimer, Parkinson, and Friedreich, who defined narcolepsy and delirium tremens? This blog is therefore a chance to celebrate the lesser known history of neurology, and to inject some fairness into the name game. Here then are 25 non-eponymous neurological diseases and the people who discovered, fully described, or named them.