When Shakespeare meets neurology: Hamlet, Ophelia and autoimmune encephalitis

Neurology can’t seem to get away from autoimmune disorders of the central nervous system. This blog has visited this topic several times before such as with the posts titled What are the dreadful autoimmune disorders that plague neurology? and What’s evolving at the cutting-edge of autoimmune neurology? The attraction of autoimmune neurological diseases lies in part in the ever-expanding spectrum of the antibodies and the challenging symptoms and syndromes they produce.

By Gentaur – Gentaur, Public Domain, Link

The fairly well-recognised ‘conventional’ antibodies are those against VGKC (Caspr 2 and LGI1), NMDA, and AMPA. There is however an almost endless list of less familiar antibodies such as those against glycine, adenylate kinase 5, thyroid, GABA-A receptors, α-enolase, neurexin-3α, dipeptidyl-peptidase-like protein 6 (DPPX), and myelin oligodendrocyte glycoprotein (MOG). I am however fascinated by the group of disorders caused by antibodies to metabotropic receptors. The main antibody in this group targets the metabotropic glutamate receptor 5 (mGluR5). The clinical picture with this antibody is a form of encephalitis which may manifest with prosopagnosia (difficulty recognising faces), and with the curious Ophelia syndrome.

By Benjamin WestOwn work, Public Domain, Link

Yes, you read it correctly. Ophelia syndrome is named after Shakespeare’s unfortunate Danish maiden, and it was first described by Dr. Ian Carr whose daughter, at the age of 15, developed progressive loss of memory, depression, hallucinations, and bizarre behaviour. These symptoms aptly describe Ophelia’s deluded and obsessional attraction to the equally deluded and murderous Hamlet. Ophelia syndrome is almost always associated with Hodgkins lymphoma and affects young people.

By V from Coventry, UK – Hamlet, CC BY 2.0, Link

Thankfully Ophelia syndrome is a relatively mild disease without the Shakespearean tragic ending because it has a good outcome if recognised and treated. You may explore all the autoimmune neurological disorders on neurochecklists.

The 130 interesting and unusual manifestations of HSP

The hereditary spastic paraplegias (HSP) are a diverse group of inherited disorders of the spinal cord. They may be transmitted dominantly or recessively, and through the X Chromosome. There are, at the last count, 79 different genetic forms of HSP. These are titled, rather confusingly, SPG1 to SPG79. Some forms of HSP occur more frequently than others. SPG4 […]

via The 130 interesting and unusual manifestations of HSP — Neurochecklists Updates

Who are on the line-up of the WESAN Exeter Neurology course in 2017?

The West of England Seminars in Advanced Neurology (WESAN) is an annual course convened by Neurologists at the Royal Devon and Exeter Hospital. You may check out the previous programmes listed in the blog post tilted What has the Exeter Neurology Course accomplished in the last decade. You may also learn more about WESAN in the blog post titled A short history of WESAN. 

Exeter Cathedral timelapse. Joe Dunckley on Flikr. https://www.flickr.com/photos/steinsky/894007623

The WESAN programme this year, as usual, is an exquisite balance of topics covering the spectrum of neurological specialisms. The agenda is a fine blend of new and old topics, delivered by experts at the cutting edge of their fields.


The Rougement Hotel Exeter. Robert Cutts on Flikr. https://www.flickr.com/photos/panr/5542700403

So what has WESAN lined up for 2017? Here are the topics and speakers


 Functional Neurological Disorders-The Assessment as Treatment

Jon Stone, Professor of Functional Neurology at Edinburgh


The Neurology of Amnesia

Adam Zeman, Professor of Cognitive Neurology at Exeter 


Advances in the Diagnosis of Neurogenetic Disorders

Julia Rankin, Consultant Clinical Geneticist at Exeter 


Emerging Treatable Autoimmune Disorders of the CNS

Sarosh Irani, Associate Professor of Neurology at Oxford 


Movement Disorders: A Video Presentation

Kailash Bhatia, Professor of Clinical Neurology at Queen Square 


Cold Injury in the Royal Navy

Paul Hughes, Neurologist at Haywards Heath 


Hepatitis E and the Nervous System

Harry Dalton, Consultant Hepatologist at Truro


The mTORopathies-What the Neurologist Needs to Know

Finbarr O’Callaghan, Reader in Paediatric Neuroscience at Great Ormond Street Hospital  


Refractory Epilepsy: Hope is not a Strategy

Hannah Cock, Professor of Neurology at St George’s Hospital 


Looking Back on a Career in Neurology – Some Things I Would Probably Have Done Differently

Nick Fletcher, Consultant Neurologist (rtd) at the Walton Centre 


Ganglioside Antibodies and the Landscape of Immune Neuropathies

Hugh Willison, Professor of Neurology at Glasgow 


Metabolic Muscle Diseases

Jon Walters, Consultant Neurologist at Swansea 


MS: Emerging Treatments and Treatment of Progressive Disease

Claire Rice, Consultant Neurologist at Bristol  


You may register for WESAN Exeter now

Follow WESAN on twitter: @wesanexeter

By FranzfotoOwn work, CC BY-SA 3.0, Link

What does the INPH-CrasH trial tell us about risk factors for normal pressure hydrocephalus?

Vascular risk factors in INPH: a prospective case-control study (the INPH-CRasH study) Israelsson H, Carlberg B, Wikkelsö C, et al Neurology 2017; 88:577-585 Abstract OBJECTIVE: To assess the complete vascular risk factor (VRF) profile of idiopathic normal pressure hydrocephalus (INPH) using a large sample of representative patients with INPH and population-based controls to determine the […]

via What does the INPH-CrasH trial tell us about risk factors for normal pressure hydrocephalus? — Neurochecklists Updates

The 52 variants of CMT… and their practical checklists

Jean-Marie Charcot, Pierre Marie, and Howard Henry Tooth will be confounded to see what has become of the disease they described hundreds of years ago. Charcot-Marie Tooth disease (CMT) was a simple and straightforward disease then, with easily recognisable features such as the ‘classic’ high arched foot (pes cavus), the hammer toes, and the inverted champagne glass appearance of […]

via The 52 variants of CMT… and their practical checklists — Neurochecklists Updates

Primary angiitis of the CNS: unusual presentations of a rare and dangerous disorder

Primary angiitis of the central nervous system (PACNS) is inflammation of the blood vessels of the central nervous system (stating the obvious you might say). It differs from other forms of angiitis or vasculitis, such as lupus and giant cell arteritis (GCA), which respect no boundaries. PACNS is as dangerous a neurological disorder as they come, and just as rare. It requires aggressive, and paradoxically equally life-threatening, immunosuppressive treatment. Between the devil and deep blue sea-that’s exactly where the neurologist managing a patient with PACNS will be found.

BRAINADE! the Brain Grenade. Emilio Garcia on Flikr. https://www.flickr.com/photos/lapolab/11929014084
BRAINADE! the Brain Grenade. Emilio Garcia on Flikr. https://www.flickr.com/photos/lapolab/11929014084

The clinical features of PACNS are unfortunately very non-specific and include headaches, seizures, stroke, and cognitive changes. This makes PACNS is a challenge to diagnose. Even when suspected, PACNS may evade detection even by the special scan of the blood vessels called angiography. More frequently, the only certain way of confirming this disease in life is with a brain biopsy. Did I say ‘certain’? I take that back. Alas, even brain biopsy is not guaranteed to make the diagnosis of PACNS. A high degree of confidence and teeth-gritting is therefore an absolute requirement in any neurologist unfortunate enough to come face-to-face with this menace.

By The original uploader was Glitzy queen00 at English Wikipedia - Transferred from en.wikipedia to Commons., CC BY-SA 3.0, Link
By The original uploader was Glitzy queen00 at English Wikipedia – Transferred from en.wikipedia to Commons., CC BY-SA 3.0, Link

To make complicated matters even worse for the unwary neurologist, there are now reports suggesting that PACNS presents in even rarer and atypical ways. For the neurological Sherlocks and Poirots, here are 2 unusual presentations of PACNS.

Isolated spinal cord involvement

Spinal Cord 2. Green Flames 09 on Flikr. https://www.flickr.com/photos/greenflames09/116396742
Spinal Cord 2. Green Flames 09 on Flikr. https://www.flickr.com/photos/greenflames09/116396742

This is a case report from the Journal of Neurology of a 44-year old woman who presented with PACNS but with purely spinal cord involvement and completely sparing the brain. The diagnosis in this case was only confirmed with a spinal cord biopsy. The authors reviewed the literature and only found 8 previous reports of PACNS beginning in the spinal cord, and half of these progressed to involve the brain. 

Unilateral cerebral presentation

Keep Left. Howard Lake on Flikr. https://www.flickr.com/photos/howardlake/4440588147
Keep Left. Howard Lake on Flikr. https://www.flickr.com/photos/howardlake/4440588147

Most cases of PACNS evenly involve both sides of the brain. This report, again from Journal of Neurology, bucks this trend with the report of a 55-year old man who had PACNS which only involved the left side of his brain. This unilateral hemispheric PACNS is a reminder that an entity called focal PACNS exists.


Do you have any sightings of unusual cases of PACNS? Please drop a comment