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.
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.
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.
The levels of NfL in serum strongly correlate with the levels in cerebrospinal fluid (CSF) of people with MS.
People with more active and more severe MS had higher levels of NfL.
People with MS on disease modifying treatment (DMT) had lower NfL levels than those who were not on treatment.
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“.
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“.
This is surely one of neurology’s bug bears, the old chestnut. Just when one generation of neurologists thinks it has buried and sealed it in an impervious crypt, it resurrects to haunt the next breed. This cyclical and macabre dance of migraine and PFOs evokes a sense of deja vu every time it comes around. And each spawn of neurologists predictably picks up the gauntlet, answers the call to arms, and sets out to slaughter the ghost of migraines past.
But let’s take a step back to basics with some definitions. The foramen ovale is just a ‘hole in the heart‘ between the right and left atria, or upper heart chambers. It is essential in foetal life because it enables circulating blood to bypass the superfluous foetal lungs (apologies to readers across the Atlantic for the superfluous ‘o’!). However, after birth, when blood needs to circulate through the now indispensable lungs, the foramen ovale becomes irrelevant. In most people, the foramen ovale humbly accepts its fate, crawls to a corner, and closes shop. But foramen ovales in some people are recalcitrant; standing their ground, they endure and survive as PFOs.
It is not clear how the myth started, but stories of migraine cure following surgical closure of PFO spread rapidly and widely. Very soon, migraineurs where demanding echocardiograms to check if they have PFOs lurking in their tickers. Research trials investigating this issue started as a trickle, and very soon become a flood. But rather than shed light, the conflicting results intensified the darkness. That is, until some indignant and determined neurologists and cardiologists set out to settle the matter once and for all. And the onslaught came in three waves of studies.
The second wave was a study published in the European Heart Journal by Heinrich Mattle and colleagues. In their PRIMA trial (Percutaneous Closure of PFO in Migraine with Aura), they blindly allocated or randomized half of their subjects with refractory migraine and PFO to have PFO closure surgery. And their verdict was, PFO closure did nothing to reduce the frequency of migraine.
Regular visitors to this blog know that we love catchy article titles. It is always heartwarming to see how some authors create imaginative and inventive headlines. This skill involves the ability to play with words, and the capacity to be double-edged. This is why this blog keeps a lookout for fascinating neurology titles. And in line with this tradition, and in no particular order of inventiveness, here are 15more catchy neurology titles!
This paper, for some unfathomable reason, set out to ask if the public knows the difference between what psychiatrists and psychologists actually do. And the authors discovered that “there is a lack of clarity in the public mind about our roles”. More worryingly, or reassuringly (depending on your perspective), they also found out that “psychologists were perceived as friendlier and having a better rapport“. Not earth-shattering discoveries, but what a great title!
Optical coherence tomography (OCT) is a cool tool which measures the thickness of the retinal fiber layer (RFL). And it has the habit of popping its head up in many neurological specialties. In this case, the specialty is multiple sclerosis, and the subject is how OCT influences its diagnosis and surveillance. Surely a window into the brain is easier to achieve than one into the soul.
The homonculus is the grotesque representation of the body on the surface or cortex of the brain. This paper reviews how formidable neurosurgeons such as Wilder Penfield worked out the disproportionate dimensions of this diminutive but influential man. He (always a man for some reason) has giant hands, a super-sized mouth, very small legs, and a miniature trunk. The clever brain doesn’t readily allocate its resources to large body parts that perform no complex functions! But be warned, this article is no light-weight reading!
This title is a play on words around MR-guided focussed ultrasound surgery (MRgFUS), an emerging technique for treating disorders such as essential tremor and Parkinson’s disease (PD). This review looks at the controversial fuss that this technique has evoked.
This paper explores the interesting subject of delusional misidentification syndromes (DMSs). The authors argue that few concepts in psychiatry can be as confusing as DMSs. And they did an excellent job of clearing our befuddlement around delusions such as Capgras and Fregoli. Very apt title, very interesting read.
This title belongs to a review of trypanosomiasis, aka sleeping sickness. It is a superb play on words, one that evokes several levels of meaning. It is simple and yet complex at the same time. Great imagination.
This paper discusses two parts of nervous system that are affected by toxoplasmosis. Playing on the symbolic contradiction between intellect and strength, the authors show how toxoplasmosis is an ecumenical abuser: it metes out the same fate to both brain and brawn.
Nitrous oxide, or laughing gas, is now “the seventh most commonly used recreational drug”. But those who pop it do so oblivious of the risk of subacute combined degeneration. This damage to the upper spinal cord results from nitrous oxide-induced depletion of Vitamin B1 (thiamine). Not a laughing matter at all!
Dopamine transport (DaT)scan is a useful brain imaging tests that helps to support the diagnosis of Parkinson’s disease and other disorders which disrupt the dopamine pathways in the brain. It is particularly helpful in ruling out mimics of Parkinson’s disease such as essential tremor. When to request a DaT scan is however a tricky question in practice. This paper, with its Shakespearean twist, looks at the reliability of DaT scans.
It should be no surprise if Shakespeare rears his head more than once in this blog post. Not when the wordsmith is such a veritable source of inspiration for those struggling to invent catchy titles. This paper looks at taupathy, a neurodegeneration as tragic as Hamlet. It particularly comments on an unusual taupathy, one induced by traumatic brain injury. Curious.
What better way to call attention to a serious complication than a catchy title like this one. This paper highlights the neurological complications of coarctation of the aorta, a serious congenital cardiovascular disease. And the key concerns here are the risks of stroke and cerebral aneurysms. Cardiologists, mind the brain!
This paper reviews the unexpected biochemical links between diabetes and Parkinson’s disease. And this relationship is assuming a rather large dimension. Why, for example, are there so many insulin receptors in the power house of Parkinson’s disease, the substantia nigra? A sweet curiosity.
The foraman ovale is a physiological hole-in-the-heart which should close up once a baby is born. A patent foramen ovale (PFO) results when this hole refuses to shut up. PFOs enable leg clots to traverse the heart and cause strokes in the brain. This paper reviews the evidence that surgically closing PFOs prevents stroke. Common sense says it should, but science demands proof. And the authors assert that they have it all nicely tied up. Hmmm.
This comes from an editorial in Lancet Neurology urging a joint approach to preventing stroke and dementia, a strategy the author calls ‘the lowest hanging fruit in the fight against these two greatest threats to the brain’. He argues that ‘at the moment, the fruit might be hanging too low for our gaze, and we are wrongly fixated on the distant future of Alzheimer’s disease treatment. We might have to stoop to conquer‘.
This opinion piece in Practical Neurologytakes a stab at the age-old neurological test of sensory impairment. Subject are asked to stand up and try to maintain their balance with their eyes shut. The author asserts that this, the Romberg’s test, ‘lacks essential specificity’, ‘risks physical injury’, and is ‘redundant’. He argues that there are much better, and safer, ways of testing for sensory ataxia. There goes an interesting test!
This is from a case report of a 69-year old man in the journal Neurology. He presented with unusual crying spells which turned out to be dacrystic (crying) seizures. This case is eventually revealed to be a case of….sorry, no spoilers. Click on the link to find out.
I am no fan of Game of Thrones, but it is an in-your-face television series which provides the setting for this catchy title. The mechanistic target of rapamycin (mTOR) pathway is underlies the pathology of tuberous sclerosis. It is therefore the target of many therapeutic strategies in the form of mTOR inhibitors. And the 4 kingdoms? You have to read the piece from the New England Journal of Medicine…perhaps after you have watched the TV series!
Statins are famous, and their fame lies in their ability to bust cholesterol, the villain in many medical disorders such as heart attack (myocardial infarction) and stroke. Some may add that statins are infamous, and this is partly because of their side effects such as muscle pain. Love them or hate them, we can’t get away from statins…even as the debate rages about their benefits and downsides.
It is not surprising therefore that the statin debate will filter into neurology. The sticking point here however has nothing to do with cholesterol busting, but all to do with whether statins increase or reduce the risk of developing Parkinson’s disease (PD). Strange as it may seem, statins and PD have a long history. And a positive one generally, I hasten to add. There is a large body of evidence to suggest a protective effect of statins on PD as reflected in the following studies:
The authors of this paper set out to investigate ‘the controversy surrounding the role of statins in Parkinson’s disease’. In this retrospective analysis of over 2,000 people with PD, and a similar number of control subjects, theauthors found that statins significantly increased the risk of developing PD. This is clearly a conclusion looking for a fight!
I must admit I was totally unaware there was any controversy about statins and PD. I was therefore curious to find out what studies are out there fuelling it. Which other trials have bucked the trend and reported an increased risk of PD from statins? And where best to find the answers but in PubMed, the repository of all human knowledge! And I found that there were only a few studies that did not report a protective effect of statins on PD, and these studies concluded, quite reasonably, that they found no relationship between PD and statins. Here are a few of the studies:
These papers reporting the absence of evidence seem happy to engage in an amicable debate to resolve the question.
One study however stood out like a sore thumb because it positively reported a negative effect of statins on PD (try and work that out!). This 2015 study, also published in Movement Disorders, is titled Statins,plasmacholesterol, and risk of Parkinson’s disease: a prospective study. The paper concludes that “statin use may be associated with a higher PD risk, whereas higher total cholesterol may be associated with lower risk“. Not only are the authors arguing that statins are bad for PD, they are also suggesting that cholesterol is good! This is a paper that was itching for fisticuffs.
What is a jobbing neurologist to do? What are the millions of people on statins to do? Whilst awaiting further studies, I will say stay put. Go with the bulk of the evidence! And keep track of TheSimvastatin Trial, funded by TheCure Parkinson’s Trust. This trial is looking at the benefit of statins in slowing down PD. And surely, very soon, the science will lead to a resolution of the argument-all you need to do is keep track of everything PD in Neurochecklists.
Primary angiitis of the central nervous system (PACNS) is inflammation of the blood vessels of the central nervous system (stating the obvious you might say). It differs from other forms of angiitis or vasculitis, such as lupus and giant cell arteritis (GCA), which respect no boundaries. PACNS is as dangerous a neurological disorder as they come, and just as rare. It requires aggressive, and paradoxically equally life-threatening, immunosuppressivetreatment. Between the devil and deep blue sea-that’s exactly where the neurologist managing a patient with PACNS will be found.
The clinical features of PACNS are unfortunately very non-specific and include headaches, seizures, stroke, and cognitive changes. This makes PACNS is a challenge to diagnose. Even when suspected, PACNS may evade detection even by the special scan of the blood vessels called angiography. More frequently, the only certain way of confirming this disease in life is with a brain biopsy. Did I say ‘certain’? I take that back. Alas, even brain biopsy is not guaranteed to make the diagnosis of PACNS. A high degree of confidence and teeth-gritting is therefore an absolute requirement in any neurologist unfortunate enough to come face-to-face with this menace.
To make complicated matters even worse for the unwary neurologist, there are now reports suggesting that PACNS presents in even rarer and atypical ways. For the neurological Sherlocks and Poirots, here are 2 unusual presentations of PACNS.
Isolated spinal cord involvement
This is a case report from the Journal of Neurology of a 44-year old woman who presented with PACNS but with purely spinal cord involvementand completely sparing the brain. The diagnosis in this case was only confirmed with a spinal cord biopsy. The authors reviewed the literature and only found 8 previous reports of PACNS beginning in the spinal cord, and half of these progressed to involve the brain.
Unilateral cerebral presentation
Most cases of PACNS evenly involve both sides of the brain. This report, again from Journal of Neurology, bucks this trend with the report of a 55-year old man who had PACNS which only involved the left side of his brain. This unilateral hemispheric PACNSis a reminder that an entity called focal PACNS exists.
Do you have any sightings of unusual cases of PACNS? Please drop a comment
Neurologists spend most of their time diagnosing benign conditions which are curable or treatable, or at least people learn to live with. Every now and then we see people with startling symptoms such as coma, convulsions, neck stiffness, or paralysis. These are obviously concerning to patients and their families who have a foreboding of diseases such as meningitis, epilepsy, and stroke. Serious as these disorders are, they at least announce themselves and show their hands. Many other neurological symptoms unfortunately give no hint of the serious diseases that follow in their trail. That is when things get a bit tricky.
What are these seemingly benign symptoms which jolt neurologists out of their blissful complacency? What are these red flag symptoms that pretend they are grey? Here are my 7 deceptively ominous neurological signs everyone should know about.
7. A numb chin
This must be the most deceptive sinister symptom in neurology. Not many people will rush to their doctors to complain about a numb chin, but it is a symptom that makes neurologists very nervous. This is because the chin gets its sensory supply from the mandibular branch of the fifth cranial nerve, also called the trigeminal nerve because it has three branches. And neurologists know that, for some bizarre reason, cancers from other parts of the body occasionally send deposits to this nerve. The numb chin syndrome is therefore not to be treated lightly.
6. Muscle twitching
OK, don’t panic yet. We have all experienced this; a flickering of an overused and tired muscle; a twitching of the odd finger; the quivering of the calf muscles in older people. Neurologists call these fasciculations, and they are only a concern if they are persistent, progressive, and widespread. And also usually only if the affected muscles are weak. In such cases neurologists worry that fasciculations are the harbingers of sinister diseases, particularly motor neurone disease (MND), better known in America as amyotrophic lateral sclerosis (ALS) or Lou Gehrig disease. Many people with muscle twitching will however have nothing seriously wrong with them, and many will be shooed out of the consulting room with the label of benign fasciculations syndrome (we love our syndromes, especially when they are benign). There are many other causes of fasciculations, but MND is clearly the most sinister of them all.
5. Transient visual loss
Neurologists often ask people with headache if their vision blurs or disappears for brief periods of time. These visual obscurations are not as dramatic as the visual loss that accompanies minor strokes or transient ischaemic attacks (TIAs). Visual obscurations affect both eyes and last only a few seconds. They are the result of sudden but brief increases in an already elevated pressure in the head. This may occur with relatively benign conditions such as idiopathic intracranial hypertension (IIH), but it may also portend a serious disorder such as a brain tumour.
4. Sudden loss of bowel or bladder control
Loss of control down there would surely concern many people, but often not with the urgency it deserves. There are many non-neurological causes of bowel or bladder incontinence, but a sudden onset suggests that it is arising from the nervous system. The worrying diagnoses here are spinal cord compression and spinal cord inflammation (transverse myelitis). These disorders are often associated with other symptoms such as leg stiffness and weakness, but I really wouldn’t wait until these set in before I ask to see a neurologist.
3. Saddle anaesthesia
Whilst we are on the topic of things down there, a related sinister symptom is loss of sensation around the genitals and buttocks, something your doctor will prudently call saddle anaesthesia. This arises when the nerves coming off the lower end of the spinal cord, collectively called the cauda equina, are compressed. The unpalatable condition, cauda equina syndrome (CES), worries neurologists because the compression may be due to a tumour in the spinal canal.
PS: The bicycle saddle is an apt analogy, but if you prefer horseriding, below is an alternative image to soothe your hurt feelings.
2. A painful droopy eyelid
A droopy eyelid is a deceptively benign symptom which worries neurologists. This symptom, which neurologist prefer to call ptosis, is particularly concerning if it is accompanied by double vision. One worrying disorder which causes ptosis is myasthenia gravis (MG), and this presents with ptosis on both sides. More sinister is ptosis which is present only on one side, particularly if it is painful. This may be caused by brain aneurysms, especially those arising from a weakness of the posterior communicating artery (PCOM) artery. As the aneurysm grows, it presses on the third cranial or oculomotor nerve, one of three nerves that controls the eyeballs and keeps the eyelids open. An aneurysm is literally a time-bomb in the brain as they wield the threat of bursting and causing a catastrophic bleeding around the brain. This makes ptosis an ominous, but also a helpful, neurological symptom.
There are many other causes of ptosis including Horner’s syndrome, so don’t panic yet but get that eyelid checked out if it refuses to straighten out.
1. Thunderclap headache
A thunderclap headache is a symptom that means exactly what it says on the label! Neurologists will ask if the onset felt as if one was hit by a cricket bat. Even though most people have never been so assaulted, almost everyone with thunderclap headache readily agree this is what it feels like. It is such a distressing symptom that it doesn’t strike the afflicted person (pun intended) that their doctors are more concerned about investigating them, then they are in curing their headache. They patient is rushed to the CT scanner, and then subjected to a lumbar puncture. The doctors then heave a huge sigh of relief when the spinal fluid shows no blood or blood products, reassured that the patient has not suffered a subarachnoid haemorrhage (SAH) from a ruptured a brain aneurysm. The patient, who now has just another headache, is left to get to grips with their now, suddenly, very uninteresting symptom. There are many other causes of a thunderclap headache, but a ruptured aneurysm is the most sinister. If you develop a thunderclap headache, don’t wait to see a neurologist…just get to the nearest hospital!
PS: Don’t feel aggrieved if you are across the Pacific; it is also a thunderclap headache if it felt like being hit by a baseball bat!
Neurology is a broad specialty covering a staggering variety of diseases. Some neurological disorders are vanishingly rare, but many are household names, or at least vaguely familiar to most people. These are the diseases which define neurology. Here, in alphabetical order, is my list of the top 60 iconic neurological diseases, with links to previous blog posts where available.
The Neurology Lounge has a way to go to address all these diseases, but they are all fully covered in neurochecklists. In a future post, I will look at the rare end of the neurological spectrum and list the 75 strangest and most exotic neurological disorders.