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.
Neurology embodies some of the most dreadful diseases known to man. Every neurological disorder is disheartening, each characterised by unique frustrations for patients and their families. It is difficult to quantify the distress and misery these afflictions impose on their victims, and even harder to appreciate the despair and anguish they evoke in those who care for them.
It is clearly hard to compare the impact of different neurological diseases. Some neurological disorders however stand out because of the consternation their names evoke, and the terror that follows in their wake. These diseases come with unimaginable physical and psychological burdens, and crushing demands on human and material resources. They impose either a debilitating morbidity, or a hasty mortality.
The nervous system ailments in the list below pose exacting therapeutic challenges, resistant as they are to all attempts at treatment or cure. This list sets out to emphasise the urgency for neuroscience to find a remedy for each of them, but it does not intend to belittle the horror of the disorders omitted from it. The choice of the number 13 is, sadly, self-evident. Here then are the top 13 most dreadful neurological disorders…all with gold links to the associations helping to defeat them.
Ataxia, in lay terms, is incoordination. This typically manifests as an unsteady gait and clumsiness. Ataxia converts all activities of daily living into burdensome chores. Whilst many types of ataxia are preventable or reversible, primary ataxias are progressive and carry a dismal outlook. In this category are Spinocerebellar ataxia (SCA), Friedreich’s ataxia, and Ataxia telangiectasia. You may read more about ataxia in these previous blog posts:
Brain cancers hardly need any description. They are either primary, arising from the brain cells, or metastatic, spreading to the brain from other organs. Some primary brain cancers, such as meningiomas and pituitary tumours, are, relatively, treatable. Many others are unfortunately ominously malignant. The most dreadful in this category is surely the spine-chilling glioblastoma multiforme. You may check out these previous blog posts for more on these tumuors:
Peripheralneuropathy is ubiquitous in the neurology clinic. Neuropathy may result from reversible situations such as overindulgence in alcohol, uncontrolled diabetes, or Vitamin B12 deficiency. Neuropathy is often just a minor inconvenience when it manifests with sensory symptoms such as tingling and numbness. It may however be debilitating when it presents as limb paralysis, or complicated by major skeletal deformities. At the severe end of the spectrum of neuropathy are the hereditary forms such as CharcotMarie Tooth disease (CMT) and Familialamyloid polyneuropathy. Read more in these blog posts:
CJD is the most iconic of the prion diseases. These disorders are as horrendous as they are enigmatic, defying categorisation as either infections or neurodegenerative diseases. More puzzling is their ability to be either hereditary and acquired. CJD exists in the classic or variant form, but both share a relentlessly rapid course, and a uniformly fatal end. You may read more in these previous blog posts titled:
Dystonia marks its presence by distressing movements and painful postures. At its most benign, dystonia is only a twitch of the eyelid (blepharospasm) or a flicker of one side of the face (hemifacial spasm). At the extreme end, it produces continuous twisting and swirling motions, often defying all treatments. The causes of dystonia are legion, but the primary dystonias stand out by their hereditary transmission and marked severity. Read more on dystonia in these blog posts:
Huntington’sdisease is an iconic eponymous neurological disorder which is marked by the vicious triumvirate of chorea, dementia, and a positive family history. It is an awful condition, often driving its victims to suicide. It is a so-called trinucleotide repeat expansion disorder, implying that successive generations manifest the disease at an earlier age, and in more severe forms (genetic anticipation). You may read more on HD in the previous blog post titled:
Also known as Amyotrophiclateral sclerosis (ALS), MND is simply devastating. Recognising no anatomical boundaries, it ravages the central and peripheral nervous systems equally. MND creeps up on the neurones and causes early muscle twitching (fasciculations) and cramps. It then gradually devours the nerves resulting in muscle wasting, loss of speech, ineffectual breathing, and impaired swallowing. Our previous blog posts on MND are:
Multiple sclerosis is a very common disease, and gets more common the further away you get from the equator. It is the subject of intense research because of the devastation it foists on predominantly young people. Many drugs now ameliorate, and even seem to halt the progression of, relapsing remitting MS (RRMS). This is however not the case with primary progressive MS (PPMS) which, until the introduction of ocrelizumab, defied all treatments. There are many contenders vying for the cause of MS, but the reason nerves in the central nervous system inexplicably lose their myelin sheaths remains elusive. You may read more on MS in these blog posts:
Rabies, a rhabdovirus, is a zoonosis-it is transmitted to man by a wide range of animals such as dogs, bats, racoons, and skunks. It is the quintessential deadly neurological disease, popularised by the Steven King book and film, Cujo. Rabies manifests either as the encephalitic (furious) or the paralytic (dumb) forms. It wreaks havoc by causing irritability, hydrophobia (fear of water), excessive sweating, altered consciousness, and inevitably death. Whilst there are vaccines to protect against rabies, a cure has eluded neuroscientists. This blog is yet to do justice to rabies but it is, at least, listed in the post titled What are the most iconic neurologicaldisorders? But you could better by checking neurochecklists for details of the clinicalfeatures and management of rabies.
Nothing is quite as heart-wrenching as the sudden loss of body function that results from spinal cord trauma. This often causes paralysis of both legs (paraplegia), or all four limbs (quadriplegia). This life-changing disorder is often accompanied by loss of control over bowel and bladder functions, and complications such as bed sores and painful spasms. You may read about the heroic efforts to treat spinal cord injury in the blog posts titled:
Tetanus is an eminently preventable disease, now almost wiped out in developed countries by simple immunisation. It however continues its pillage and plunder in the developing world. It strikes young and old alike, often invading the body through innocuous wounds. Tetanus is caused by tetanospasmin and tetanolysin, the deadly toxins of the bacterium Clostridium tetani. The disease is classified as generalised, localised, cephalic, or neonatal tetanus. It is characterised by painful spasms which manifest as lockjaw (trismus), facial contortions (risus sardonicus), trunkal rigidity (opisthotonus), and vocal cord spasms (laryngospasm). The disease is awfully distressing and, when advanced, untreatable. It is a stain on the world that this avoidable disorder continuous to threaten a large number of its inhabitants. Check neurochecklists for more on the pathology,clinicalfeatures, and management of tetanus.
As for all lists, this will surely be subject to debate, or perhaps some healthy controversy. Please leave a comment.
Huntington’s disease (HD) is, without doubt, one of the most dreaded neurological disorders. It is named after George Huntington, but the first description is probably by Charles Oscar Waters in 1842. It is dominantly inherited, each child carrying a 50% chance of acquiring the faulty gene. The genetics is slightly tricky because HD is also a tricnucleotide repeat expansion disorder, similar to some other neurological diseases such as Friedreich’s ataxia (FA), Kennedy disease, myotonic dystrophy, spinocerebellar ataxia (SCA), and oculopharyngeal muscular dystrophy (OPMD). In these diseases, a section of the genetic code duplicates itself repeatedly, producing abnormally long segments; worse still, these segments get longer which each transmission down the family line. This is called genetic anticipation, and it leads to later generations of the family developing the disease at an earlier age, and manifesting it more severely.
HD is not a nice disease. It is accompanied by chorea, probably the most distressing abnormal movement to torment the human body. This is a continuous, writhing muscle activity which involves all the body, and generating very grotesque and painful postures. As if this wasn’t enough, dementia eventually sets in, as does almost every other neurological symptom one could imagine. HD is a problem neurology needs to solve. And thankfully there is some activity in that direction. Here are 4 recent hope-raising developments.
1. Gene silencing with ISIS-HTTRx
The manufacturers of ISIS-HTTRx must surely be rueing the unfortunate choice of name for their gene silencing drug. But they will take comfort in its promise to crush HD. It is the first trial of a new drug for HD, and it is touted as probably ‘one of the most important developments since the gene for Huntington’s disease was discovered‘. ISIS-HTTRx neutralises huntingtin, the toxic product which accumulates in, and damages, the nerves of people with HD. The only snag…it has to be delivered directly into the spinal fluid. I’m sure an oral tablet will eventually follow, but ISIS-HTTRx is still a long way off; it has to be tested in human volunteers first. One eye then on Sarah Tabrizi, the trial lead, and the other eye on the drug’s name; ISIS pharmaceuticals is now IONIS.
CYP46A1 is an enzyme which regulates the breakdown of cholesterol. And what has cholesterol got to do with HD? Well…wait for this…cholesterol accumulates in the nerve cells of people with HD, and may contribute to nerve damage. The good news is that CYP46A1 helps to get rid of cholesterol, and some researchers postulate that medicines which enhance the activity of CYP46A1 will improve HD. This all comes from a paper in the journal Brain titled CYP46A1, the rate-limiting enzyme for cholesterol degradation, is neuroprotective in Huntington’s disease. We are still at the proof of concept stages, but it will help if the CYP46A1-enhancing drugs come as handy pills!
4. Controlling chorea with deutetrabenazine
Neurologists are familiar with tetrabenazine, the best treatment for chorea. And Star Trek fans are familiar with the heavy hydrogen atom, deuterium. Put the two together and, voila, you get deutetrabenazine (SD809). The heavy hydrogen of deuterium makes deutetrabenazine a more stable drug. This should make it last longer in the body, and also cause less side effects. Considering that the adverse effects of tetrabenazine include depression and parkinsonism, this is not an insignificant advantage (pardon the double negative…I couldn’t help it).
How well does deutetrabenazine translate to clinical practice? Sufficiently well enough it seems, going by the trial published in JAMA Neurology titled Effect of Deutetrabenazine on Chorea Among Patients With Huntington Disease. The authors compared the drug to placebo and showed that deutetrabenazine effectively improved chorea at 12 weeks. It is not surprising that the trial compared deutetrabenazine to placebo rather than the existing alternative; head-to-head drug trials are as rare as hen’s teeth in medicine (I wonder why that is). Anyway, deutetrabenazine may be coming to a pharmacy near you soon…we hope.
There is still a long way to go yet, but each small step is a glimmer of hope for a neurodegenerative disease such as HD.
Remember, you can have everything HD at your fingertips with neurochecklists(and pardon the shameless pitch).
Shortly after posting this blog I came across these articles on HD prospects
From Huntington’s Disease News comes Pridopidine. One more to add to the hope for neuroprotection against HD.
From the Hazard Gazette comes SIRT2as a future treatment target for HD
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.
This is a follow-up to my previous blog post, So what is remarkable about neurology anyway? That post reviewed the challenging tasks neurologists face everyday. How do they go about it? How do they evaluate their patients with suspected neurological disorders?
For the uninitiated, the process of the neurological assessment must seem like an outlandish ritual. Unlike cardiologists who approach patients with the familiar stethoscope, neurologists come armed to the hilt with an arsenal of threatening equipment. Patients are often bewildered, and occasionally irritated, with the neurological exam. Admitted, they sometimes, they sometimes emerge from the assessment feeling battered and bruised-all for a good cause of course!
So what are these bizarre deeds that marks the neurological consultation?
1. Neurologists welcome you with an overly firm handshake
The handshake is a valuable neurological tool. It tells the neurologist right from the beginning if there is any weakness or if there is a form of muscle stiffness called myotonia. Therefore avoid the neurologist’s handshake if you suffer with arthritis or other painful hand conditions.
2. Neurologists make you do the catwalk
The way you walk, the gait, may show the neurologist a variety of clues or signs. There are a variety of abnormal gaits that often point to a diagnosis even before the consultation actually begins. Examples include the shuffling gait in Parkinson’s disease, the hemiparetic gait in Stroke, and the waddling gait in diseases that give rise to hip girdle weakness. More embarrassing for some patients is that the neurologist may actually ask them to do a catwalk, all for the sake of making a diagnosis you must understand!
Other bizarre associated tests are walking an imaginary tightrope, standing on one leg, standing on tip toes and then on the heels, and marching in one spot with eyes shut
3. Neurologists stare intently at you
The face often give the neurologist the clue to many diagnoses. Conditions such as Bell’s palsy and Stroke are evident from the face as are Parkinson’s disease, myotonic dystrophy and facio-scapulo-humeral muscular dystrophy (FSHD). There’s no need to blush therefore when the intent gaze seems to go on endlessly.
4. Neurologists come up very close- to peer into your soul
If the eyes are the windows to the soul, then neurologists are second only to ophthalmologists in recognising this nebulous entity. The back of the eye, or retina, holds a variety of valuable clues for many neurological diseases. The neurologist typically looks for signs of increased pressure in the head and this may occur with brain tumours, meningitis, encephalitis, This may also occur without any obvious cause in a condition called idiopathic intracranial hypertension (IIH). Other eye signssuch as cataracts and pigmented retina seen with disorders for example mitochondrial diseases.
To peer into the soul, the neurologist may come very uncomfortably close, (hoping the aftershave isn’t too strong and that the morning deodorant has lasted till then). Don’t hold your breath however, as this gazing into the soul may take longer than you anticipate.
5. Neurologists ask you to roll your eyes-in all sorts of directions
Abnormal eye movements are key pointers to many neurological disorders. There are six muscles that move each eyeball, and these are under the control of three pairs of cranial nerves-the oculomotor, the trochlear, and the abducens nerves. These nerves in turn are coordinated by complex nerve cell bodies or nuclei in the brain stem.The eyelids and pupils are also muscles under control of nerves.
These cranial nuclei coordinate a symphony of unparalleled and unimaginable complexity. This allows us to focus on moving objects without any hinderance. Things may go wrong with this symphony, and this typically results in double vision (diplopia) and droopy eyelids (ptosis). Diseases that cause these symptoms include brain aneurysms,myasthenia gravis (MG), and brainstem stroke. Some diseases may cause the eyeballs to move in uncontrollable and chaotic ways called nystagmus, oscillopsia, and opsoclonus(neurologists love these names!)
Don’t be shocked therefore when your neurologist asks you to look up, look down, look to the right and left; to follow this or the other hand; to look at this fist then at these fingers…. It’s all a helpful game-honest!
6. Neurologists ask you to pretend to brush your teeth
Your neurologist may request you to brush your teeth or hair with an imaginary brush, or ask you to do victory sign or the thumbs-up sign (never thumbs-down mind you). Almost verging on the comedic, this is a serious test because these simple tasks are impaired in many diseases. The difficulty in performing tasks one has previously been proficient at is called dyspraxia, or apraxia if the ability is completely lost. Without any weakness or numbness, people with dyspraxia are unable to use common tools and equipment, reporting that they have no idea how to manipulate them. This could be seen in some forms of stroke and some dementias. Do decline however if she asks you to mimic the great mime Marcel Marceau.
7. Neurologists ask you to wiggle your tongue and poke it out
The tongue is a very important muscle and holds countless clues for the neurologist. It is innervated by the last of the 12 cranial nerves, the hypoglossal nerve. which may be paralysed by a very localised stroke and this is often in the context of a condition called cervical artery dissection. This is a tear in one of the big arteries in the neck which take blood to the brain. The tear may arise from trivial neck movements and manipulations such as look up for a long time or staying too long on the hairdressers couch. A clot then forms at the site of the tear, and this then migrates to block a smaller blood vessel supplying the brainstem where the hypoglossal nerve sets off from…phew! Anyway, when this kind of stroke occurs, the tongue deviates to the the weaker side when it is poked out.
The more general weakness of the tongue is seen in conditions such as motor neurone disease (MND),in which the tongue also quivers at rest-something neurologists call fasciculations. The cheeky neurologist (pun intended) will ask you to push against her finger through your cheek to test its full strength.
Another problem that may affect the tongue is myotonia, a condition in which he tongue and other muscles are stiff and relax very slowly after they are activated. To test this, your neurologist may actually tap on your tongue, and then watches in fascination as it stiffens and then relaxes very slowly. Strong but slow moving tongues may be seen in Parkinson’s disease (PD). So, when next your neurologist says ‘open up’, he really means business.
8. Neurologists flex their muscles against yours
OK, she will not literally wrestle you to the ground but it may appear so at times. Pushing against your head, pressing down against your elbows, leaning hard against your leg-she will do everything to show she is stronger than you. Only if she fails will she score your power as grade 5/5-the best you can get. If you do not score full marks however you place the neurologist in a bit of a quagmire; a score between 0-5 is not always easy to allocate, and the obsessive neurologist may get in a bind and may give you marks such as 3+ or 4-. Just for fun let her win, and see her consternation!
9. Neurologists hit you with a hammer-in all sorts of places
The reflex hammer is perhaps the most well-recognised tool of the neurologist. These hammers come in all shapes and sizes, and some are really quite scary. People expect to have their knees tapped and look forward to what they have seen many times on TV-the leg kicking out. Most patients find this amusing. They are however often surprised when the neurologist proceeds to use the hammer on their jaw, elbow, wrist and ankles. The then often bristle at having the soles of their feet stroked by the end of the hammer’s handle, a sharp uncomfortable end it is. All the hammer does is to stretch the tendons of muscles, and this elicits a reflex that causes the muscle to contract or tighten up. This response may be exaggerated (hypereflexia) if there is any problem in the central nervous system. Conversely the reflex response may be diminished (hyporeflexia) with problems of the peripheral nervous system. Stroking the foot is called the Babinski response and gives a similar form of information to the neurologist. But beware the neurologist who then proceeds to stroke the side of your foot or squeeze your shins, all in an effort to get the same information-it is really an unnecessary and uncomfortable duplication of tests.
10. Neurologists prick and prod you with a sharp pin
Now this must take the cake, and quite rightly often comes at the end of the neurological examination. As threatening as this tests appears, this is probably the neurologist at his most acute. Using a sterile pin, the neurologist asks you to respond ‘yes’ if the sensation you perceive is sharp, and ‘no’ if it is dull. He then carefully proceeds to map out areas of reduced sensation or feeling, frowning as he struggles to keep track of your responses in his mind. He tries to establish if you have a glove and stocking pattern of sensory loss seen in peripheral neuropathy (nerve end damage). It may also be a dermatomal pattern seen with radiculopathy (trapped nerve in the spine). Unfortunately for the neurologist however many patients do not understand the rules of the game and give all sorts of unimaginable responses; not surprising when one is under the threat of a sharp pointy object!
These are but a few of the bizarre doings of neurologists. Seeing a neurologist soon? Be prepared-you have been warned!
PS. Images used in this blog post are for illustration purposes only and do not necessary depict the actual equipment used by neurologists. The examination steps described are however a good reflection of actual neurological practice.