I can’t seem to get away from the theme of Mozart and epilepsy. When I first looked at this, in a blog post titled Mozart and seizures? The links between epilepsy and music, I took the topic rather lightly, more a subscript than a headline you may say. But I have since learnt to take the links between epilepsy and music more seriously.
The major trigger for my ‘road to Damascus’ conversion is a 2018 paper titled Study of the Mozart effect in children with epileptic electroencephalograms, published in the journal Seizure. The paper was an eye-opener because it gave a very helpful comprehensive context to the broader beneficial effect of music…not just in epilepsy, but in other neurological disorders such as Parkinson’s disease, dementia and sleep disorders. The authors, Elyza Grylls and colleagues, started on the established premise that Mozart’s music has a beneficial effect on epilepsy. What they wanted to know was if other forms of music have a similar settling effect on epilepsy, or if only Mozart’s music carries the magic touch. The authors therefore played Mozart’s Sonata for two pianos in D major (K448) to 40 children with epilepsy who were undergoing an EEG (electroencephalogram, or electrical brain wave test). They then compared this with the effect of playing other types of music. Remarkably, they found that only Mozart’s Sonata led to a significant reduction in EEG epileptic discharges.
The authors concluded that there was indeed an anti-epileptic effect of Mozart’s music, the so-called ‘Mozart therapy’. But what is so special about K448? They speculate that it has to do with the structure of Mozart’s music, containing as it does, long periodicities. Interestingly, the music of Yanni, which is similarly structured, has somewhat a similar effect on brain wave activity. On the contrary, and sorry to Beethoven fans, Fur Elisedoesn’t have this effect.
By Bionerd – MRI at Charite Mitte, Berlin (used with permission), CC BY 3.0, Link
You have surely wondered by now whether K448 is the only one of Mozart’s compositions to have an anti-epileptic effect. It doesn’t matter if you haven’t, because the authors of another interesting paper have. They titled their study, published in 2018, Mozart’s music in children with drug-refractory epileptic encephalopathies: comparison of two protocols. Published in the journal Epilepsy and Behaviour, the authors,Giangennaro Coppola and colleagues, compared the effect of K448 with a set of his other compositions. Intriguingly they found that the composition set actually had a greater effect in epilepsy than K448…by a wide margin of 70% to 20%! Furthermore, the set was better tolerated by the children; they were less irritable and had a better nighttime sleep quality.
So, is it all rosy in the garden of music and the brain? No, it’s not! As every rose grows on a thorny tree, so do some forms of music trigger epileptic seizures. This so-called musicogenic epilepsy is well-recognised, and two recent culprits are the music of Sean Paul, discussed in the journal Scientific American , and the music of Ne Yo, explored by NME. Therefore you should craft your playlist wisely.
Adult attention deficit hyperactivity disorder (ADHD) is a key psychiatric disorder. It is characterised by some core clinical featureswhich are hyperactivity, inattention, impulsivity, disorganisation, and low stress tolerance. People with ADHD have several life impediments that characterise their day-to-day lives; these include difficulty starting tasks, struggling to prioritise, and failing to pay attention to details. Enduring chaotic lifestyles, they struggle to keep up with their academic, employment, and relationship commitments.
For the public and for most physicians, ADHD is recognised only as a childhood disorder. But 10-60% of childhood onset ADHD persist into adulthood. Furthermore, about 4.5% of adults have ADHD. The failure to recognise ADHD as an adult problem therefore means it is easily missed in adult psychiatry and neurology clinics. Referring to this in a review published in the journal Psychiatry (Edgmont), David Feifel labelled adult ADHD as the invisible rhinoceros (you must read the article to understand why it is not the elephant in the room). Concerned that many adults with ADHD are misdiagnosed as suffering with anxiety or depression, he urged psychiatrists to routinely screen for adult ADHD in every adult presenting with these disorders.
The scale of the failure to diagnose adult ADHD was emphasised by Laurence Jerome in a letter to the Canadian Journal of Psychiatry. Titled Adult attention-deficit hyperactivity disorder is hard to diagnose and is undertreated, his letter highlighted the finding of the US ADHD National Comorbidity Survey which concluded that most adults with ADHD have ‘never been assessed or treated’. He argued that this oversight places heavy lifetime burdens on adults with ADHD such as impaired activities of daily living, academic underachievement, poor work record, marital breakdown, and dysfunctional parenting. A great burden indeed, but a preventable and treatable one!
How is all this psychiatry relevant to the general neurologist? Well, many manifestations of ADHD are the stuff of the neurology clinic. Cognitive dysfunction for example is prevalent in adult ADHD, and it may present to the neurologist as impaired short term memory, executive dysfunction, impaired verbal learning, and, of course, impaired attention. Sleep related disordersare also frequent in adult ADHD, and these include excessive daytime sleepiness (EDS), restless legs syndrome (RLS), periodic leg movements of sleep (PLMS), and cataplexy. There are also several other neurological co-morbidities of adult ADHD such as epilepsy and learning disability.
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).
By uncredited – Images from the History of Medicine (NLM) [1], Public Domain, https://commons.wikimedia.org/w/index.php?curid=11648572Today, 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.
This new group of neurological diseases is threatening to disrupt the easy distinction between several neurological disorders such as myasthenia gravis (MG), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and Guillain Barre syndrome (GBS). It even includes the newly described IgLON 5 antibody disorder, something I blogged about asIgLON5: a new antibody disorder for neurologists. You may explore IgG4-related disorders in this paper titled The expanding field of IgG4-mediated neurological autoimmune disorders.
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.
Zika virus is another novel infection with prominent neurological manifestations. We are learning more about it every day, and you may check my previous blog post on this, titled 20 things we now know for certain about the Zika virus.
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.
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.
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.
But why is a neurologist talking about seahorses. It’s all in the name. The Latin name for seahorse is hippocampus , derived from hippos for horse, and kampos for sea monster. Where biologists saw fish, the ancients saw monsters. And you really can’t blame them…take a closer look
Neurologists are passionate about the hippocampus for various reasons. In people with memory complaints, for example, hippocampal atrophy may predict the development of Alzheimer’s disease . A shrunken hippocampus is also seen in some forms of epilepsy. Neurologists thereforeendlessly harangue their neuroradiology colleagues to look closely at their patients’ brain MRI scans, and to tell them that the hippocampus is shrunken…even if it’s just a little bit smaller. Unfortunately for the neuroradiologists, the MRI scans do not come colour-coded as in the illustrative scan below.
This blog post is however about major depression, and not about epilepsy or dementia. Depression, that bad feeling we all feel every now and then is frustrating, but major depression is devastating. And we now know that it is accompanied by major alterations in the structure of the brain. And, yes, the changes are in the hippocampus. I got interested in this subject when I came across a piece in Neurology News reporting that people with depression have a smaller hippocampus.
The association of depression with hippocampal atrophy is however an old one. Proceedings of the National Academy of Science (PNAS) reviewed the relationship in an editorial from 2011 titledDepression, antidepressants, and the shrinking hippocampus. The author addressed the unresolved puzzle…which of the two came first. Reminiscent of the chicken and egg scenario, it is not clear if the hippocampal atrophy causes depression, or vice versa. To add to the puzzle, the paper conjectured the possibility of a third, unknown agent, causing both the depression and the small hippocampus.
This question was the focus of a meta-analysis published in Molecular Psychiatry this year. It reviewed the brain imaging data of 15 studies, involving about 1700 people with major depression. Titled Subcortical brain alterations in major depressive disorder, the authors confirmed the link between depression and hippocampal atrophy, and also showed that the shrinkage is worse in those who developed depression at an early age, and in those who have had frequent episodes of depression.
Does depression lead to hippocampal atrophy? The meta-analyses hinted so, but there were too many caveats for the authors to arrive at a definitive conclusion. They admit that more needs to be done to unravel depression….leaving the mystery of the shrinking seahorses to continue to another day.
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.
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.
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.
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.
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!
There was a recent, very concerning report about the reliability of functional MRI (fMRI) software. This raised doubts about the veracity of all fMRI research carried out over decades. Thankfully Neuroskeptic addressed this issue headlong in a post titled False positive functional MRI hits the mainstream. The blog pointed out that fMRi software concerns are not new, and importantly, they are not serious enough to invalidate 15 years of research. Phew! The post also discussed the retraction and anti-retraction story that somehow missed the headlines. And who is Neuroskeptic? You need to check out another blog on pseudnymous bloggers to find out.
2. From: Brainfacts.org
What could be more tantalising than a blog post titledThe neuroscience of violence? This post, by Douglas Fields, discusses the discovery of the neuronal rage circuit, and how neuroscientists can now manipulate this. The post says “…with the flip of a switch neuroscientists can launch an animal into a violent attack or arrest a violent battle underway by activating or quelling the firing of specific neurons in the brain’s rage circuits”. Add the hypothalamic attack region to the mix and you have a blog post worth reading.
3. From: The Stroke Blog
I admit that the question, What does “blurry vision” really mean after stroke?, has never occurred to me. This clinical post is a good reminder of all the visual symptoms that may accompany a stroke. It is quite basic but informative.
4. From: Curious Stardust
I was intrigued by this blog post by Seana Coulson titled What a Speech Disorder Reveals About Brain Function. It looks at language and its relationship to the brain and takes readers on a historical excursion of the ‘discovery’ of aphasia by Paul Broca. It details how the field has progressed since then, and sprinkled a couple of demonstrative video clips to explain the symptom.The blog refreshingly admits to how little we know about the brain:“while cognitive neuroscientists have learned quite a bit in the last 150 years about which parts of the brain are involved in different aspects of speaking and understanding language, we still don’t have a really good explanation of exactly what the cells in the left frontal lobe code for…”. Will we ever?
5. From: Beyond the Ion Channel
Neurogenetics isn’t easy but this blog makes it, at least, readable. Take this post by Ingo Helbig titled RORB in generalized epilepsy with absences–going retinoic. This explores a hormone receptor called Retinoid-Related Orphan Receptor-Beta (RORB) which plays an important role in epilepsy and neuro-developmental disorders. Not the easiest read for a layperson, but a good read anyway.
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.
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