Chronic inflammatory demyelinating polyneuropathy (CIDP) is a neurological disorder which causes loss of the fatty myelin covering of large nerves (demyelination). This slows down the speed at which the nerves can transmit electrical impulses. People with CIDP develop weakness and sensory disturbances, but not always in equal measure. CIDP is a pain for the afflicted, and a veritable nightmare for the neurologist.
The diagnostic process for CIDP includes some rather uncomfortable tests such as nerve conduction studies and lumbar puncture (spinal tap). CIDP is however a most rewarding disease to treat because many people respond to immune treatments such as steroids, intravenous immunoglobulins (IVIG), or plasma exchange (PE).
The diagnosis of CIDP is however not straightforward. The results of the tests are not always clearcut, and a lot of sifting and sorting goes into nailing the diagnosis. And even when the diagnosis is eventually made, there is a very long list of potential causes of CIDP which often require treatment on their own merit. Worryingly, some of these conditions make the treatment of CIDP difficult. And this is where IgG antibodies play a nasty role in CIDP.
Neurologists are now recognising that a subset of people with CIDP have IgG4 antibodies which greatly influence the clinical presentation and the treatment of CIDP. Anti-contactin antibody is one such antibody, but by far the most important is anti-neurofascin 155 (NF155). What do we know about this antibody? How does it influence the course of CIDP? To answer these questions, below are 10 important things we now know about CIDP associated with anti-NF155.
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
This is a quick post to highlight changes and proposed changes to some neurological terms. It is not unusual for such changes to occur every now and then. We have, for example, seen benign intracranial hypertension (BIH) changed to idiopathic intracranial hypertension (IIH), and Hallavorden Spatz disease transformed into pantethonate kinase associated neurodegeneration (PKAN).
Anti VGKC antibody encephalitis is caused by two different antibodies called LGI1 and Caspr2. The immunology laboratory would however only test for these two if the ‘generic’ VGKC test is positive. Neurologists are understandably left scratching their heads when both tests turn out to be negative. Not any more, going by a report in Neurology titled The relevance of VGKC positivity in the absence of LGI1 and Caspr2 antibodies. The judgment is out: a positive VGCK antibody test is not significant if both LGI1 and Caspr2 are negative. What a relief.
Many acquired neurological disorders have a way of dragging genetics into their fold. Such is the case it seems with anti NMDA receptor encephalitis. This is the case with the GRIN-1 gene which codes for an NMDA receptor subunit. Mutations in this gene results in visual impairment, intellectual disability, and eye movement disorders. This is reported in Neurology by Josep Dalmauand colleagues in a paper titled Delineating the GRIN1 phenotypic spectrum. It is appropriate that the authors call this the genetic sibling of NMDA receptor encephalitis.
4. ECT for anti-NMDA receptor encephalitis
The typical treatment of autoimmune encephalitis revolves around steroids, intravenous immunoglobulins (IVIg), and plasma exchange. Neurologists, when pushed to the wall, may use heavy duty agents such as Rituximab and Cyclophosphamide. Because anti-NMDA receptor encephalitis may be associated with ovarian teratomas, neurologists may make the difficult trip across the border to consult their gynaecology colleagues. I thought these were all the treatment options for anti NMDA receptor encephalitis until I read this case report, again in Neurology, which reported an excellent response to Electroconvulsive therapy in anti-NMDA receptor encephalitis. A no-brainer then if you see neurologists exchanging pleasantries with psychiatrists: they are the ECT experts. It is just a case report for now, but well-worth thinking about when all else fails.
Neurologists have always known that autoimmunity accounts for many nervous system disorders. A classical example is Sydenham’s chorea or St Vitus dance. This movement disorder develops after rheumatic fever, and is caused by antibodies to the bacterium called Streptocccus. The modern-day resurrection of this condition is called paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. I know, too long, but just call it PANDAS. A great acronym I must say, quite unlike ABGA which stands for anti basal ganglia antibody syndrome, an umbrella term for many movement disorders provoked by external agents.
A third group of neurological diseases are more sinister because the antibodies are generated by cancer cells. These paraneoplastic neurological syndromes are legion and protean, requiring a high index of suspicion to diagnose. Most frustrating for neurologists is that the cancer itself may not emerge for several years after the diagnosis of a paraneoplastic syndrome. Notorious for this cloak and dagger behaviour is small cell lung cancer (SCLC). Because of the potential consequences, neurologists deploy their heavy duty imaging scans such as positron emission tomography (PET) scans. They then lie low, year after year, waiting to nab the devious cancer as soon as it shows up.
In recent years, a completely different class of disorders has attained notoriety and infamy in the form of autoimmune encephalitis. These disorders often pretend to be infectious diseases, but they totally disregard the antibiotics and antiviral agents the neurologist attacks them with. By subterfuge and subversion they disable ion channels and receptors to cause havoc in the brain. And nobody has described such havoc better than Susannah Cahalan in her book Brain on Fire: My Month of Madness.
Autoimmune encephalitis may fester for weeks, years or decades, evading detection by its duplicitous behaviour, and by the increasing number of antibodies that may be responsible. There are however three main culprit antibodies which neurologists are now getting a grip on:
These conditions are all potentially fatal but eminently curable; this underlies the importance of recognising and treating them very early. A recent paper in Lancet Neurology summarises the clinical approach to autoimmune encephalitis(pdf).
Autoimmune neurology is a rapidly evolving field. I will review recent developments in this area in a second post to follow shortly titled What’s breaking at the cutting edge-of autoimmune neurology?