Giant cell arteritis (GCA) is a nasty inflammatory disorder that affects the large arteries. Because it characteristically involves the temporal artery, this form of vasculitis is also referred to as temporal arteritis. It usually affects people over the age of 50 years and manifests with sudden onset headache, scalp pain, and a thick, tender temporal artery. GCA is often accompanied by polymyalgia rheumatica (PMR) , a painful condition of the joints and muscles. The active systemic inflammation in GCA is often detected by the erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) tests. These distinguishing features constitute most of the diagnostic criteria for GCA.
Most people with GCA however do not have all the ‘classical’ features of the disease. A high index of suspicion is therefore required to sniff out the duplicitous miscreant. It is particularly imperative to make the diagnosis as early as possible to prevent the dreaded complications of GCA, sudden blindness and stroke. The treatment of GCA, implemented according to established treatment guidelines, involves several months of oral steroids, drugs which cause immune suppression and a host of other side effects. It is therefore essential that the diagnosis of GCA is made correctly to avoid putting the patient on a long, risky, and unnecessary treatment.
What then is the value of the temporal artery biopsy in the diagnosis of GCA? This is the question posed by Bowling et al in their incisive paper titled Temporal artery biopsy in the diagnosis of giant cell arteritis: does the end justify the means?They reviewed 129 temporal artery biopsies and found that the clinical diagnosis of GCA was confirmed in only 13% of cases. Furthermore, the outcome of the biopsy rarely ever influenced the treatment; 87% of those with a normal biopsy result still continued their treatment. The miffed authors therefore rhetorically, and indignantly, asked: “can we justify invasive surgery to all patients on histological grounds when the results may not alter management?”
This is an entirely reasonable question especially because there are other more accurate and less invasive ways of establishing the diagnosis of GCA. These include:
But the answer to the authors’ rhetorical question is anyones guess. It is a sad tradition of medicine that studies such as these take ages to change practice. Indeed I predict the the temporal artery biopsy will sidestep this minor hurdle and simply continue its long and agonising reign. Despair!
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.
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.
At first, it seemed like a single drop, but it is quickly turning into a trickle. The first inkling was a study of >1,700 people with motor neurone disease (MND) which was published in the journal Neurology titled Depression in amyotrophic lateral sclerosis. The authors found that depression is a very frequent diagnosis shortly before people are diagnosed with MND.
Surely a coincidence, I thought. A rogue finding, or even an understandable response to illness. My excuses were however debunked by another paper published soon after in the Annals of Neurology. Titled Psychiatric disorders prior to amyotrophic lateral sclerosis, the study found that depression may precede the diagnosis of MND by more than 5 years. The authors also report a high frequency of other psychiatric conditions preceding the diagnosis of MND, such as anxiety and psychosis.
And just off the press is this report from Nature Communications titled Genetic correlation between amyotrophic lateral sclerosis and schizophrenia. What do we make of this? Is this just the tip of the iceberg? Surely more studies are needed before any firm conclusions. Perhaps this may lead to some early biomarker that enables neurologists to stop the process of progression to full blown MND. Perhaps.
Prophetic it seems, as I am here forced to revisit the topic because I came across a few recent interesting reports on the neurology of gluten.
Take this case report from Nutrients titled gluten psychosis: confirmation of a new clinical entity. The article comes with some good references that suggest it will do no harm to check anti-gliadin antibodies in people with unexplained psychosis. I do wonder how one case report would confirm an entity such as gluten psychosis, but there you are.
Gluten-induced visual impairment
The second item is another case report published in Journal of Neurology titled severe, persistent visual impairment associated with occipital calcification and coeliac disease. The subject of the case report has long-standing coeliac disease and visual impairment. Her brain MRI scan showed calcifications in the visual area, evidence the authors claim, of celiac disease causing brain calcifications …..and thereby causing the patients visual loss. Is it just a case of correlation rather than causation? But there you are.
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is as complicated to articulate, as it is to manage. CIDP is the result of an inflammatory attack against myelin, the fatty layer that encases large nerves. The damage to the myelin sheath considerably slows down the speed at which nerves transmit electrical impulses. This leads to limb weakness, sensory impairment, and a host of other symptoms.
The diagnosis of CIDP is made on the basis of a clinical examination, nerve conduction studies (NCS), spinal fluid analysis, and countless blood tests. If this convoluted diagnostic process is hair-tearing, the treatment is even more perplexing.
There are 2 major CIDP treatment conundrums. The first is whether to start the treatment with steroids, or with intravenous immunoglobulins (IVIg). The second conundrum is what to do when the patient fails to respond to both of these first line CIDP treatments. Two recent papers have now come to the rescue, and they hope to settle, once and for all, these two major neurological puzzles.
1. Choosing steroids or IVIg as 1st line treatment
The first line treatment for CIDP is usually a toss-up between steroids and intravenousimmunoglobulins (IVIg). This is because neurologists had no way of telling who will do well on steroids, and who will respond to IVIg. Until now, that is. A recent report in the Journal of Neurology, Neurosurgery and Psychiatry (JNNP) set out to understand what patient characteristics predict response to IVIg. The authors studied >200 people with CIDP treated with IVIg, and reported that 1/4 did not respond. These IVIg non-responders had the following features:
The presence of pain
Association with other autoimmune diseases
A difference in the severity of weakness between the arms and the legs
The absence of anti-myelin associated glycoprotein (anti-MAG)
The authors conclude that people with CIDP who have the features above should start their treatment with steroids rather than IVIg. This surely beats tossing a coin.
2. Choosing rituximab as 1st line treatment
Choosing the 2nd line treatment of CIDP is comparatively easy; swap between IVIG and steroids, or go for plasma exchange (PE). Rituximab, a monoclonal antibody, is now also recognised as an effective treatment for CIDP. Conventional practice is to use this expensive treatment only when both IVIg and steroids fail. A recent paper however suggests that people with CIDP who also have IgG4 antibodies do not respond to either IVIg or steroids. On the bright side however, they do well when treated with Rituximab. The paper in the journal Neurology is titled Rituximab in treatment-resistant CIDP with antibodies against paranodal proteins. The authors studied only 4 patients, but the number was enough for them to suggest that patients with CIDP, who also have IgG4 antibodies, should be treated with Rituximab. Makes sense to me, if the alternative is predictable failure.
Now that some light has been shone on the treatment of CIDP, the next stage is to see how things work at the coal face. Do you have any feedback on CIDP treatment? Please leave a comment.
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