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.
When it comes to imaging the nervous system, nothing but an MRI will do for the fastidious neurologist. CT has its uses, such as in detecting acute intracranial bleeding, but it lacks the sophistication to detect or differentiate between less glaring abnormalities. It also comes with a hefty radiation dose. MRI on the other hand, relying on powerful magnetic fields, is a ‘cleaner’ technology.
MRI scans on their own are however often insufficient to sate the craving of the neurologist for precision. A plain MRI scan, for example, will not tell if a multiple sclerosis lesion is old or new, and it may fail to detect subtle but significant lesions such as low grade brain tumours or lymphoma. Many lesions on routine MRI scan are also ill-defined and non-specific, and could pass for abscesses, vasculitis, inflammation or just small vessel disease (wear and tear) changes.
To silence the niggling doubts, the neurologist often requests an MRI scan with contrast. The idea is to use a dye to separate the wheat from the chaff, the active lesions from the silent ones. This works because sinister lesions have a bad and dangerous habit of disrupting the blood brain barrier. All such insurgencies across the hallowed BBB is sacrilege, a sign that something serious is afoot, (or is it underfoot?). Contrast dyes, on the other hand, are adept at detecting these breaches, traversing them, and staining the sinister lesion in the process. This stain appears on the MRI scan as contrast enhancement. MRI with contrast is therefore invaluable, and a positive study is a call to arms.
Without any doubt, gadolinium is the favoured dye for contrast MRI scans. Gadolinium (Gd) is a lanthanide rare earth metal and it is one of the heavier elements of the periodic table with atomic number 64. It is named after the thrice-knighted Finnish chemist Johan Gadolin, who also discovered the first rare earth metal, yttrium.
We know a lot about some of the risks of injecting gadolinium into the body, such as its tendency to accumulate in people with kidney impairment (who cannot excrete it efficiently). We also know that it may cross the placenta to damage the developing baby. These are however hazards with simple and straight-forward solutions: avoid gadolinium in pregnancy, and don’t use it in people with poor renal function.
Much more challenging is the problem of gadolinium deposition in the brain of people with normal renal function. This is concerning because it is unpredictable, and because it has the potential to compromise brain structure and function. This blog has previously asked the question, “Is gadolinium toxic?“. The question remains unanswered, andregulatory agencies are still studying the data to provide guidance to doctors. Patient groups on the other hand have been up in arms, as one would expect, impatiently waiting for answers. What then is the state of play with gadolinium? Should neurologists and their patients really be worried? Below are 8 things we now know about gadolinium and its potential brain toxicity.
1. Gadolinium deposition is related to its insolubility at physiological pH
The toxic potential of gadolinium is thought to be the result of its insolubility at physiological pH. Furthermore, gadolinium competes against calcium, an element fundamental to cellular existence. This competition is obviously detrimental to the body.
2. The less stable gadolinium agents are the most toxic
There are two forms of gadolinium based contrast agents (GBCAs): the less stable linear GBCAs, and the more stable macrocyclic GBCAs. The linear GBCAs are more toxic, of which Gadodiamide (Omniscan)stands out. Other linear agents are gadobenate dimeglumine (MultiHance), gadopentetate dimeglumine (Magnevist), gadoversetamide (OptiMARK), gadoxetate (Eovist), and gadofosveset (Ablavar). The macrocyclic GBCAs, even though safer, are not entirely blameless. They include gadobuterol (Gadavist), gadoterate meglumine (Dotarem), and gadoteridol (ProHance). Therefore, choose your ‘gad’ wisely.
3. Gadolinium deposits in favoured sites in the brain
It is now established that gadolinium deposits in three main brain areas. The most favoured site is the dentate nucleus of the cerebellum. Other popular regions are the globus pallidus and the pulvinar. This deposition is, paradoxically, visible on plainT1-weighted MRI scans where it shows as high signal intensity.
4. The risk of deposition depends on the number of injections
The risk of gadolinium deposition in the brain is higher with multiple administrations. Stated another way, and to stretch this paragraph out a bit longer, the more frequently contrast injections are given, the higher the chances gadolinium will stick to the brain. The possible risk threshold is 4 injections of gadolinium. The fewer the better…obviously!
5. Gadolinium also deposits outside the brain
The favoured site of gadolinium deposition outside the brain is the kidney, where it causes nephrogenic systemic fibrosis, a scleroderma-like disorder. This however occurs mostly in people with renal impairment. Gadolinium also deposits in other organs outside the brain including bone, skin, and liver. (Strictly speaking, this item has nothing to do with the brain, but it helped to tot up the number to 8 in the title of this blog post, avoiding the use of the more sinister se7en).
6. Harm from gadolinium brain deposition has not been established
8. There are emerging ways to avoid gadolinium toxicity
The safest use of gadolinium is not to use it at all. There are some developments in the pipeline to achieve this, although probably not in the very near future. Such developments include manganese based contrast agents such as Mn-PyC3A. A less definitive option is to mitigate the effects of gadolinium by using chelating agents; two such potential agents are nanoparticlesand 3,4,3-LI(1,2-HOPO).
Why not get the snapshot view of gadolinium toxicity in the neurochecklist:
The Neurology Lounge strives hard to keep to the straight and narrow path of clinical neurology. But every now and then it takes a peek at what is happening at the cutting edge of neuroscience. And what can be more cutting edge then biomarkers, with their promise of simplifying disease identification, making prompt and accurate diagnosis an effortless task.
The quintessential biomarker however remains as elusive as quicksilver. Not that one could tell, going by the rate biomarkers are being spun from the neuroscience mills. Biomarkers are the buzz in many neurological fields, from brain tumours to multiple sclerosis (MS), from Alzheimer’s disease (AD) to Huntington’s disease (HD).
The proliferation of contending biomarkers is however probably highest in the field of motor neurone disease (MND). Is there a holy grail out there to enable the rapid and accurate diagnosis of this relentlessly progressive disease? There is clearly no dearth of substances jostling for prime position in the promised land of MND biomarkers. Below is a shortlist of potential MND CSF biomarkers; just click on any to go to the source!
Biomarkers elevated in the cerebrospinal fluid (CSF)
Some general neurologists get away with not having to think too much about multiple sclerosis (MS). This is because they have an ‘MSologist‘ at hand to refer all their patients with ‘demyelination‘. Many general neurologists however care for people with MS because they do not have a ‘fallback guy‘ to do the heavy lifting for them. This therefore makes it imperative for neurologists to keep up with everything about this often disabling and distressing disorder.
The management of MS is however very tricky, and it is challenging to get a grip of it all. This is partly because the clinical course is varied, and the diagnostic process tortuous. The patient first goes through an onerous retinue of tests which include an MRI, a lumbar puncture, evoked potentials, and a shedload of blood tests. This is all in a bid to secure the diagnosis and to exclude all possible MS mimics.
Then comes the head-scratching phase of determining if the patient actually fulfils the diagnostic criteria for MS, or if they just have clinically isolated syndrome (CIS) and radiologically isolated syndrome (RIS). To secure the diagnosis of MS, the neurologist turns to the McDonald criteria which stipulate dissemination in time and place of inflammatory events. As simple as this should be, this is no easy task at all. This is because, at different times, the criteria have meant different things to different people. The guidelines have also gone through several painful, and often confusing, iterations. Indeed the McDonald criteria have only recently been re-revised-to the delight of MSologists but the chagrin of the general neurologist!
Once the diagnosis of relapsing remitting MS (RRMS) is reasonably established, the patient is taken through a guided tour of the ever-expanding available treatment options. These are typically to prevent relapses, but more recently to prevent disease progression as well. People with mild to moderate MS are nudged towards interferons, glatiramer acetate, dimethylfumarate, or terifluonamide. Those with more aggressive disease, on the other hand, are offered a menu of fingolimod, natalizumab, or alemtuzumab. Other newer agents include daclizumab and cladribine. And, just stepping into the arena, there is ocrelizumab for primary progressive (PPMS). Whichever option is chosen, the course of treatment is long, and it is fraught with risks such as infections and immune suppression.
Once the bigger questions have been settled, the neurologist then braces for the ‘minor’ questions her enlightened patients will ask. The easier questions relate to the treatment of symptoms, and some of the most vexing concern the role of Vitamin D deficiency. Such questions include, ‘Is vitamin D deficiency a cause of MS?‘, ‘Do people who are vitamin D deficient experience a worseoutcome?‘, and ‘Should patients with MS be on Vitamin D supplementation?‘.
To attempt to resolve these questions I plunged into some of the literature on Vitamin D and MS. And this is like opening Pandora’s box. Here are some of the things I found.
It therefore appears that there is an association of vitamin D deficiency with MS, but it is far from certain that this is a causative relationship. One hypothesis is that vitamin D deficiency is the outcome, rather than the cause, of MS. The deficiency presumably results becuase the very active immune system in people with MS mops up the body’s Vitamin D. This so-calledreverse causation hypothesis asserts thatvitamin D deficiency is a consumptive vitaminopathy.
Even if Vitamin D deficiency doesn’t cause MS, the evidence suggests that it negatively influences the course of the disease.
What to do?
This is the million dollar question eloquently posed by a recent editorial in the journal Neurology titled Preventing multiple sclerosis: to (take) vitamin D or not to (take) vitamin D?The reasonable consensus is to encourage vitamin D replenishment to prevent MS, starting from preconception. It is also generally agreed that people with MS should be on vitamin D supplementation in the expectation that it will slow the disease activity.
A practical approach to Vitamin D replacement is the Barts MS team vitamin D supplementation recommendation. This is to start with 5,000IU/day vitamin D, and aim for a plasma level of 100-250 nmol/L. Depending on the level, the dose is then adjusted, up or down, to between 2-10,000IU/day. They also advise against giving calcium supplementation unless there is associated osteoporosis.
What is a general neurologist to do? To follow the prevailing trend, and hope it doesn’t change direction too soon!
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.
What is it about neurological inflammatory disorders that makes them so rebellious? Why do they defy convention and disregard their defining features. I discussed a similar phenomenon in my previous blog post titled Why is neuromyelitis optica (NMO) endlessly surprising neurology? NMO refused to play by the rules and was punished by having it’s named changed to NMOSD. Perhaps it’s time for CLIPPERS to suffer the same fate….starting with a shorter acronym perhaps?
Medical futurists predict that scientific advances will lead to more precise definition of diseases. This will inevitably result in the emergence of more diseases and fewer syndromes. This case is made very eloquently in the book, The Innovators Prescription. Many neurological disorders currently wallow at the intuitive end of medical practice, and their journey towards precision medicine is painfully too slow. Neurology therefore has a great potential for the emergence of new disorders.
In the ‘good old days’, many diseases were discovered by individual observers working alone, and the diseases were named after them. In this way, famous diseases were named after people such as JamesParkinson, Alois Alzheimer, and GeorgeHuntington. For diseases discovered by two or three people, it didn’t take a great stretch of the imagination to come up with double-barrelled names such as Guillain-Barre syndrome (GBS) or Lambert-Eaton myasthenic syndrome (LEMS).
Today, however, new diseases emerge as a result of advances made by large collaborations, working across continents. These new diseases are named after the pathological appearance or metabolic pathways involved (as it will require an act of genius to create eponymous syndromes to cater for all the scientists and clinicians involved in these multi-centre trials). This is unfortunately why new disorders now have very complex names and acronyms. Take, for examples, chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) and chronic relapsing inflammatory optic neuropathy (CRION). It is a sign that we should expect new neurological diseases to be baptised with more descriptive, but tongue-twisting, names.
New disease categories emerge in different ways. One is the emergence of a new disorder from scratch, with no antecedents whatsoever. Such was the case with autoimmune encephalitis, a category which has come from relative obscurity to occupy the centre stage of eminently treatable diseases. I have posted on this previously as What’s evolving at the cutting edge of autoimmune neurology and What are the dreadful autoimmune disorders that plague neurology?Other disease categories form when different diseases merge into a completely new disease category, or when a previously minor diseases mature and stand on their own feet. These are the stuff of my top 8 emerging neurological disorders.
This huge monster is ‘threatening’ to bring together, under one roof, diverse disorders such as tuberous sclerosis complex, epilepsy, autism, traumatic brain injury, brain tumours, and dementia. You may explore this further in my previous blog post titled mTORopathy: an emerging buzzword for neurology.
4. Hepatitis E virus related neurological disorders
A field which is spurning new neurological disorders is neurological infections, and Hepatitis E virus (HEV) is in the forefront. We are now increasingly recognising diverse Hepatitis E related neurological disorders. HEV has now been linked to diseases such as Guillain Barre syndrome (GBS) and brachial neuritis. And the foremost researcher in this area is Harry Dalton, a hepatologist working from Cornwall, not far from me! And Harry will be presenting at the next WESAN conference in Exeter in November 2017.
Multisystem proteinopathy is a genetic disorder which affects muscles and bone, in addition to the nervous system. It is associated with Paget’s disease of the bone and inclusion body myositis, with implications for motor neurone disease (MND) and frontotemporal dementia (FTD). Quite a hydra-headed monster it seems, all quite complex, and perhaps one strictly for the experts.
7. GLUT-1 deficiency syndromes
GLUT-1 stands for glucose transporter type 1. Deficiency of GLUT-1 results in impaired transportation of glucose into the brain. GLUT-1 deficiency syndrome presents with a variety of neurological features such as dystonia, epilepsy, ataxia, chorea, and a host of epilepsy types. It starts in infancy and is characterised by a low level of glucose and lactic acid in the cerebrospinal fluid. Expect to hear more on this in the near future.
8. Progressive Solitary Sclerosis
And this is my favourite paradigm shifter. Neurologists often see people with brain inflammatory lesions and struggle to decide if they fulfil the criteria for multiple sclerosis (MS). The current threshold for concern is when there have been two clinical events consistent with inflammation of the nervous system, or their MRI scan shows involvement of at least two different sites of the nervous system. Well, dot counting may soon be over, going by this paper in Neurology titled Progressive solitary sclerosis: gradual motor impairment from a single CNS demyelinating lesion. The authors identified 30 people with progressive clinical impairment arising from a single inflammatory nervous system lesion. The authors were convinced enough to recommend the inclusion of this new entity, progressive solitary sclerosis, in future classifications of inflammatory disorders of the central nervous system. Move over progressive MS, here comes progressive SS. Neurologists will surely have their job cut out for them.
Do you have any suggestions of emerging neurological disorders? Please leave a comment