The emerging influential role of microglia in neurology

By GerryShawOwn work, CC BY-SA 3.0, Link

The most important clinical fallout of dysfunctional microglia appears to be the emergence of dementia. It is indeed speculated that microglia may hold the key to stopping the notorious Alzheimer’s disease (AD). This is because microglia seem to play a role in eliminating the amyloid plaques which are thought to contribute to the disease process. Experiments suggest that there is excessive microglial activation in AD, and these supercharged microglia destructively eat up’ synapses, the all-important junctions where nerve cells communicate with each other. It is also relevant that microglial activation is particularly prominent in the hippocampus, a structure critical for memory formation. Because synaptic loss is such a key feature of AD, it is hoped that a better understanding of microglial function may lead to therapeutic tools that modulate AD microglial activation.

Microglial cells and photoreceptors. NIH Image Gallery on Flickr. https://www.flickr.com/photos/nihgov/46571706425

Microglial activation also seems to play a role in another prominent neurodegenerative disease, Parkinson’s disease (PD). It is also speculated that microglia are activated in PD as a response to environmental triggers, and the activated microglia cause neuronal damage by producing toxic substances. Because this is presumably an inflammatory process, there is the hope that a better understanding of the process will open up new therapeutic possibilities.

Microglia. NIH Image Gallery on FLickr. https://www.flickr.com/photos/nihgov/42301918151

Another disorder in which microglia may play a pathogenetic role is frontotemporal dementia (FTD) in which chronic microglial activation has been reported. It is significant that the microglial activation is most evident in the frontal cortex as this correlates with the behavioural and speech disorders which characterise FTD. More intriguingly, the activated microglia seem to express the progranulin (PGRN) gene mutations that are known to be associated with FTD. Enough clues one might say.

By Mary AntipovaOwn work, CC BY 4.0, Link

The reach of microglial dysfunction however goes way beyond the big three of AD, PD, and FTD. For example, microglia are acutely activated in traumatic brain injury (TBI), and this may be responsible for the damage that results from this. Microglia also appear to be relevant in cerebrovascular disorders because microglial activation has been reported in ischaemic stroke and in haemorrhagic stroke. And the cherry on top is surely the report that microglia play a role in prion disorders. It may well turn out that neuroscientists are just opening up the microglial can of worms.

Abraçada de microglia Patricia Bogdanov-Cristina Sola-Joel Sampedro- Marta Valeri. Vall d’Hebron Institut de Recerca VHIR on Flickr. https://www.flickr.com/photos/vhir/31615774702

***

Want to find out more on microglia? You may want to explore these links:

Review: Microglia in motor neuron disease

Motor cortex transcriptome reveals microglial key events in amyotrophic lateral sclerosis

Which drug reduces the autoimmune risks of alemtuzumab?

Mitigating alemtuzumab-associated autoimmunity in MS: a “whack-a-mole” B-cell depletion strategy Meltzer E, Campbell S, Ehrenfeld B, et al. Neurol Neuroimmunol Neuroinflamm 2020; 7:e868. Abstract Objective To determine whether the punctuated administration of low-dose rituximab, temporally linked to B-cell hyperrepopulation (defined when the return of CD19+ B cells approximates 40%-50% of baseline levels as measured before alemtuzumab […]

Which drug reduces the autoimmune risks of alemtuzumab? — Neurochecklists Blog

What are the 695 topics that make up neurology?

The goal of Neurochecklists is to bring everything even remotely neurological under one roof. It set out to be a practical, comprehensive, easily searchable, on-the-go database. Sourcing information from reliable textbooks and journals, the database has slowly grown to peak today at >3,000 checklists spread across precisely 695 topics. These topics, in turn, are grouped […]

What are the 695 topics that make up neurology? — Neurochecklists Blog

The remarkable scope of neurology…in 83 revealing numbers

Exploring Neurochecklists is a revealing experience… It always highlights the expansive range of neurological disorders. To illustrate this extensive breadth and scope of neurology… Here are 83 striking numbers..all linked to their checklists. 83. Numbers in a city: New Haven, CT. See Ming-Lee on Flickr https://www.flickr.com/photos/seeminglee/142117353 11 neurological complications of aortic dissection 11 causes of […]

The remarkable scope of neurology…in 83 revealing numbers — Neurochecklists Blog

Which anti-MOG antibody treatment has the lowest relapse risk?

Steroid-sparing maintenance immunotherapy for MOG-IgG associated disorder. Chen JJ, Flanagan EP, Bhatti MT, et al. Neurology 2020; 95:e111-e120. Abstract Objective Myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG) associated disorder (MOGAD) often manifests with recurrent CNS demyelinating attacks. The optimal treatment for reducing relapses is unknown. To help determine the efficacy of long-term immunotherapy in preventing relapse in […]

Which anti-MOG antibody treatment has the lowest relapse risk? — Neurochecklists Blog

Is thrombolysis beneficial for central retinal artery occlusion?

Intravenous fibrinolysis for central retinal artery occlusion: a cohort study and updated patient-level meta-analysis. Mac Grory B, Nackenoff A, Poli S, et al. Stroke 2020; 51:2018-2025. Abstract Background  Central retinal artery occlusion results in sudden, painless, usually permanent loss of vision in the affected eye. There is no proven, effective treatment to salvage visual acuity […]

Is thrombolysis beneficial for central retinal artery occlusion? — Neurochecklists Blog

A few more helpful and practical neurology checklists

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

Monumental breakthroughs in the history of neuroscience

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.

By Jeff Dahl – Edited version of Image:EdSmPaPlateVIandVIIPrintsx.jpg, Public Domain, Link

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.

Achievement. Gregory Vozzo on Flickr. https://www.flickr.com/photos/revgv/32592150306

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.

By © Nevit Dilmen, CC BY-SA 3.0, Link

Brain mapping

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 HitzigGustav 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.

By BkroegerOwn work, CC BY-SA 3.0, Link

Central nerves

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.

PSA+NCAM+neuron. Jason Snyder on Flickr. https://www.flickr.com/photos/functionalneurogenesis/4573320569

Cranial nerves

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.

By OpenStax – https://cnx.org/contents/FPtK1zmh@8.25:fEI3C8Ot@10/Preface, CC BY 4.0, Link

Peripheral 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.

By BruceBlausOwn work, CC BY 3.0, Link

Nerve conduction

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.

By JanbroggerOwn work, Public Domain, Link

Chemical neurotransmission 

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.

By Doctor Jana – https://docjana.com/neuro-muscular-junction/, CC BY 4.0, Link

Special senses

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.

 

By Wiley – Wikimedia, CC BY-SA 3.0, Link

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.

Prion Proteins and Mouse Nerve Cells. NIH Image Gallery on Flickr. https://www.flickr.com/photos/nihgov/48440889002

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.

 

Compass rose. Margaret W. Carruthers on Flickr. https://www.flickr.com/photos/64167416@N03/7022634029

 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.

By OpenStax College – Anatomy & Physiology, Connexions Web site. http://cnx.org/content/col11496/1.6/, Jun 19, 2013., CC BY 3.0, Link

***

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:

Websites

Milestones in Neuroscience Research

A Short History of European Neuroscience

Books

Minds Behind the Brain

Dates in Neurology

25 non-eponymous neurological disorders… and the names behind them

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, Joseph 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.

***

Amyotrophic lateral sclerosis (ALS)

Jean-Martin Charcot

Készítette: Unidentified photographerhttp://resource.nlm.nih.gov/101425121, Közkincs, Hivatkozás

Aphantasia

Francis Galton (and Adam Zeman)

By Eveleen Myers (née Tennant) – http://www.npg.org.uk/collections/search/portrait/mw127193, Public Domain, Link

Chronic inflammatory demyelinating polyneuropathy (CIDP)

Peter J Dyck

By Dr. Jana – http://docjana.com/#/saltatory ; https://www.patreon.com/posts/4374048, CC BY 4.0, Link

Corticobasal degeneration (CBD)

WRG Gibb, PJ Luthert, C David Marsden

https://upload.wikimedia.org/wikipedia/commons/c/cd/ProteineTau.jpg

Epilepsy

Hippocrates

Hippocrates. Eden, Janine and Jim on Flickr. https://www.flickr.com/photos/edenpictures/8278213840

Essential tremor

Pietro Burresi

By UndescribedOwn work, CC BY-SA 4.0, Link

Frontotemporal dementia (FTD)

Arnold Pick

By Unknown authorhttp://www.uic.edu/depts/mcne/founders/page0073.html, Public Domain, Link

Inclusion body myositis (IBM)

E J Yunis and F J Samaha

CC BY-SA 3.0, Link

Meningitis

Vladimir Kernig and Jozef Brudzinski

By A. F. Dressler – Festschrift zum 70. Geburtstag Dr. Woldemar Kernig’s: Von Verehrern und Schülern herausgegeben als Festnummer der St. Petersburger medicinischen Wochenschrift St. Petersburger medizinische Wochenschrift, Bd. 35, Nr. 45. (1910), Public Domain, Link

Migraine

Aretaeus of Cappadocia

By Cesaree01Own work, CC BY-SA 4.0, Link

Multiple sclerosis (MS)

Jean-Martin Charcot

Journal.pone.0057573.g005http://www.plosone.org/article/info:doi/10.1371/journal.pone.0057573#pone-0057573-g005. Licensed under CC BY 2.5 via Wikimedia Commons.

Multiple system atrophy (MSA)

Milton Shy and Glen Drager

By Kenneth J. Nichols,Brandon Chen, Maria B. Tomas, and Christopher J. Palestro – Kenneth J. Nichols et al. 2018. Interpreting 123I–ioflupane dopamine transporter scans using hybrid scores., CC BY 4.0, Link

Myasthenia gravis (MG)

Samuel Wilks

By Unknown authorhttp://ihm.nlm.nih.gov/images/B25782, Public Domain, Link 

Myotonic dystrophy

Hans Gustav Wilhelm Steinert

By Unknown author – reprinted in [1], Public Domain, Link 

Neurofibromatosis

Friedreich Daniel von Recklighausen

By Unknown authorIHM, Public Domain, Link 

Narcolepsy

Jean-Baptiste-Edouard Gélineau

https://upload.wikimedia.org/wikipedia/commons/7/74/Jean_Baptiste_Edouard_G%C3%A9lineau.jpg

Poliomyelitis

Michael Underwood

By Manuel Almagro RivasOwn work, CC BY-SA 4.0, Link

Progressive supranuclear palsy (PSP)

John Steele, John Richardson, and Jerzy Olszewski

By Dr Laughlin Dawes – radpod.org, CC BY 3.0, Link

Restless legs syndrome (RLS)

Karl Axel Ekbom

By Peter McDermott, CC BY-SA 2.0, Link

Stiff person syndrome (SPS)

Frederick Moersch and Henry Woltmann

By PecatumOwn work, CC BY-SA 4.0, Link

Synesthesia

Georg Sachs and Gustav Feschner

Synaesthesia. aka Tman on Flickr. https://www.flickr.com/photos/rundwolf/7001467111/

Stroke

Hippocrates

By editShazia Mirza and Sankalp GokhaleSee also source article for additional image creators. – editShazia Mirza and Sankalp Gokhale (2016-07-25). Neuroimaging in Acute Stroke.Attribution 4.0 International (CC BY 4.0), CC BY 4.0, Link

Tabes dorsalis

Moritz Romberg

By https://wellcomeimages.org/indexplus/obf_images/39/1d/edecf5a530781f5c10603a50fa35.jpghttps://wellcomecollection.org/works/gctr3stg CC-BY-4.0, CC BY 4.0, Link

Trigeminal neuralgia

John Fothergill

By Gilbert Stuarthttp://www.pafa.org/Museum/The-Collection-Greenfield-American-Art-Resource/Tour-the-Collection/Category/Collection-Detail/985/mkey–1923/, Public Domain, Link

Tuberous sclerosis

Désiré-Magloire Bourneville

By Unknown author – Bibliothèque Interuniversitaire de Médecine – http://www.bium.univ-paris5.fr/images/banque/zoom/CIPB0452.jpg, Public Domain, Link

***

Reunion of neurologists at the Salpêtrière hospital. Photograph, 1926 https://commons.wikimedia.org/w/index.php?curid=36322408

***

Let us then celebrate the pioneers…

Eponymous and anonymous alike

7 remarkable patients who determined the course of neuroscience

It is no exaggeration to say that most progress in medicine has been achieved one unfortunate patient after another. Either by accident, or by misguided design, our understanding of human physiology and pathology have frequently come at the expense of the misfortune of countless patients, and it continues to do so. Whilst large trials teach us a lot about the characteristics of diseases, it is however the single case study that often reveals the most defining insights. For example, it was the accidental gunshot injury sustained by Alexis St Martin that led to our understanding that the gastric phase of digestion depends on the acid produced by the stomach. The gory injury resulted in a permanent fistula between St Martin’s stomach and his skin, a veritable window through which the army doctor, William Beaumont, peered to see nature at work.

By Jesse Shire Myer – A book, Life and Letters of Dr. William Beaumont …, Public Domain, Link

But enough of other organs; our interest is of course the nervous system. Who then were the tragic heroes of neuroscience, the valiant who submitted their bodies in life, and their brains in death, for the advancement of science? Who are the famous, and the infamous, in the annals of the brain? Here is our run down of 7 remarkable patients who defined the history of neuroscience.

Brain with Hands. Michael Coglan on Flickr. https://www.flickr.com/photos/mikecogh/21837053882

 

7. Patient SM

Patient SM is one of the lesser known figures in neuroscience, but her contribution to the science of emotions is immense. As someone who simply did not know what it was to experience fear, she provided the clues to the anatomical foundations of our passions. It turned out that the source of her fearlessness were lesions in her amygdala. It is little wonder that her life was characterised by risky ventures and perilous experiences, as she was incapable of detecting and avoiding danger. The amygdala is now established as the command and control centre for the emotions. One could argue, albeit unoriginally, that to lose one amygdala may be an accident, but to lose both will have to be termed a disaster. And in the case of Patient SM, her catastrophe is a result of Urbach–Wiethe disease, a disorder which destroys both amygdalas…but mercifully spares the hippocampus.

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. 次のアドレスからこのファイルで使用している画像を取得できますURL., CC BY-SA 2.1 jp, Link

6. Anna ‘O’

By Original uploader was Kaesar at it.wikipediaLink

Bertha Pappenheim, better known by her nickname ‘Anna O‘, was the seminal hysterical patient reported by Josef Breuer and Sigmund Freud. It is probably to her singular credit that the concept of hysteria became a neuroscience curiosity, even if this was on the fringes. Her constellation of symptoms will however be familiar to every neurologist: limb paralysis, speech difficulties, visual impairment, hallucinations, and episodes of loss of consciousness. It is clear that this disorder lives on, and after several iterations, now comes under the remit of functional neurological disorders (FND). It is interesting that Freud had the largely correct insight that behind many cases of hysteria lies some form of trauma.

5. Blanche Wittman

By André Brouillet – Photo prise dans un couloir de l’université Paris V, Public Domain, https://commons.wikimedia.org/w/index.php?curid=3820726

The great French neurologist Jean-Martin Charcot is not a person to be outdone by other neuroscientists, and this applies to his one-time protege, Sigmund Freud. It is therefore not surprising that in studying hysteria, he outdid Freud by finding a more remarkable subject called Blanche Wittman. She became his star attraction in the demonstrations he held at the Pitié-Salpêtrière Hospital where she performed for the great and the good of French neurology. It is in this way that she achieved abiding fame in the iconic painting of Pierre Aristide André Brouillet. Her dramatic hysterical attacks earned her the sobriquet ‘The Queen of Hysterics‘, but her contribution to the actual science of the brain is rather underwhelming. There is however no denying that she is a lasting landmark in the history neuroscience.

4. Auguste Deter

By Unknown authorUnknown source, Public Domain, Link

Whilst the name Alois Alzheimer has gone down in history for describing the fearsome dementia that bears his name, the name of the patient who made it all possible is not a household one at all. Auguste Deter was the first person to be diagnosed with the horrendous disease which still ravages mankind, and without any cure in sight. After studying her illness in life, Alzheimer had the fortune of examining her brain after her death. It is his detailed examination that revealed what we now know as the hallmarks of the disease, senile plaques and neurofibrillary tangles. It is remarkable that a recent analysis of Alzheimer’s preserved histopathological slides revealed that Auguste Deter carried the classical presenilin 1 (PSEN1) gene mutation that is associated with the disease. Can neuroscience ever be any more satisfying than that!

3. Louis Victor Leborgne

By Polygon data were generated by Database Center for Life Science(DBCLS)[2]. – Polygon data are from BodyParts3D[1], CC BY-SA 2.1 jp, Link
Yet another watershed neuroscience patient whose name doesn’t often ring any bells, or flow easily off the tongue. Leborgne’s misfortune was to develop a curious inability to speak, now recognised as expressive aphasia. He was only able to communicate with a single word, tan, and this explains his nickname, Patient Tan. Paul Broca’s fortune, on the other hand, was to study Leborgne in life, and to examine his brain after death. This singular patient made Broca a household name because this type of speech difficulty is also known as Broca’s aphasia. Broca also localised the lesion responsible for Leborgne’s aphasia, and it was in a part of the dominant hemisphere now known as Broca’s area. Two eponyms for the price of one you may say. Leborgne is also probably the turning point for the contentious concept of cerebral localisation, resurrecting it from the ashes of phrenology.

2. Phineas Gage

By Author of underlying work unknown. – File:PhineasPGage.jpg, Public Domain, Link

Phineas Gage is remarkable for achieving what few other neuroscience patient have, entry into popular folklore. The victim of a work-related accident, Gage sustained a unique form of brain injury when he was impaled by a tamping rod whilst trying to set explosions as part of his work as a rail construction worker. The explosion was accidentally set off prematurely, and the rod was propelled through Gage’s left cheek bone, through his left eye socket, and it then penetrated both frontal lobes. It was remarkable that Gage was not physically inconvenienced immediately following the accident, but surviving the whole affair was just the beginning of his real misfortune; his personality, previously calm and dedicated, became volatile and disinhibited. In relating the story of Gage, there is no getting away from a famous quotation; those who knew him before his accident pithily remarked that Gage ‘was no longer Gage‘. It is to his misfortune that we owe our understanding of the important role the frontal lobes play in regulating personality and behaviour.

 

1. Henry Molaison

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. 次のアドレスからこのファイルで使用している画像を取得できますURL., CC BY-SA 2.1 jp, Link

Known only as Patient HM throughout his life, Henry Gustav Molaison is perhaps the most important patient to ever cross the path of neuroscience. He earned this distinction on account of the profound amnesia he developed after he underwent brain surgery to control his severe epilepsy. Very bravely, his neurosurgeon, William Beecher Scoville, removed large chunks of his temporal lobes on both sides, a previously unheard of procedure. His epilepsy became largely controlled, but the aftermath was a disaster; he lost the ability to form new memories. As it has become a familiar refrain by now, Henry’s misfortune became a boon for neuroscience. He became probably the most extensively studied patient in the history of brain science; he spent the rest of his life undergoing one neuropsychological test or the other until neuroscientists obtained a thorough understanding of the anatomical and functional foundations of memory formation. Whilst the key lesson from his case is the important role of the hippocampus in memory formation, there is so much more he contributed to brain science in life. And even after death, his brain is an object of fascination for neuroscientists; they opened up his skull as soon as he died, took out his brain, and cut it up into tiny slices for further study. Henry is therefore the ultimate neuroscience patient who keeps giving even after departing this mortal coil.

Over the next few weeks I will be reviewing three excellent books on Henry Molaison in my book review blog, The Doctors Bookshelf. Why not follow me there to find out more about the remarkable man.

***

Do you want to explore more interesting neuroscience patients?

Here are 9 to satisfy your urge!

 

Elliot

Giovanni A

Jane Avril

Lelong

Little Hans

Marquis de Dampierre

Patient JP

Patient NA

Carol Jennings