The 30 most enduring neurological controversies

The World Congress of Controversies in Neurology (CONy) has been held every year since 2007, and the most recent conference was held virtually in September 2021. The longevity of the conference, and the increasingly crowded agenda, are testimonies to the range of uncertainties, and the breadth of ambiguities, that bedevil neurological practice. Imprecision and doubt pervade the management of large swathes of nervous system disorders. The huge controversies are also testament to the size of evidence-free zones encroaching on all neurological subspecialties. Over the years, CONY has provided a platform for opinionated experts to rub each other the wrong way as they defend their views and protect their turfs. CONy however also gives neutral controversy-busters an opportunity to iron out these wrinkles on neurology’s face.

Debate Energetico. Jumanji Solar on Flikr. https://www.flickr.com/photos/jumanjisolar/5371921203

Looking through the agenda of CONy over the years, some of the controversies seem to pop up with clockwork regularity; they either manifest in the same contexts, or resurrect as alternative manifestations of the same unresolved questions. It is these enduring controversies that point to the most unsettled matters in neurology. There is therefore a lesson to learn by reviewing the most contentious topics in neurology. To do this, I pored over all previous CONY conference programs and I have listed the most clinically relevant most disputed topics at the end of this blog post. It is from this list that I extracted the following 30 most enduring neurological controversies.  You may also follow the links to see the Neuochecklist take on these topics.

Raccoon argument II. Tambako The Jaguar on Flikr. https://www.flickr.com/photos/tambako/7460999402

 

1. Should clinically isolated syndromes (CIS) be treated?

2. Is Parkinson’s disease (PD) a prion disorder?

3. Should epilepsy be diagnosed after the first unprovoked seizure?

4. Should steroids or IVIg be the first-line therapy for CIDP?

5. Does cognitive reserve prevent neurodegeneration?

6. Is anti-epileptic drug withdrawal advisable after 2 years of seizure-freedom?

7. Should survivors of hemorrhagic stroke be restarted on oral anticoagulants?

8. Should disease-modifying therapies be stopped with onset of secondary progressive MS?

9. Is mild cognitive impairment a useful concept?

10. Is beta-amyloid still a relevant target in the treatment of Alzheimer’s disease (AD)?

 

 

11. Should patients with embolic stroke of undetermined source (ESUS) be anticoagulated?

12. Is intravenous thrombolysis effective in wake-up stroke?

13. Should newly diagnosed multiple sclerosis (MS) be started on aggressive therapy?

14. Do the clinical criteria of normal pressure hydrocephalus (NPH) predict response to shunting?

15. Is CSF examination necessary to diagnose multiple sclerosis (MS)?

16. Should PFO closure be a standard treatment for embolic stroke of undetermined source (ESUS)?

17. Will serum neurofilament levels replace MRI in monitoring multiple sclerosis (MS) progression?

18. Does a high number of cerebral microbleeds (CMBs) contraindicate anticoagulant treatment?

19. Is herpes virus infection a risk factor for Alzheimer’s disease (AD)?

20. Can physical trauma precipitate multiple sclerosis?

 

 

 

21. Is heavy physical exercise a risk factor for amyotrophic lateral sclerosis (ALS)?

22. Does vestibular migraine exist?

23. Is intravenous immunoglobulin (IVIg) effective in refractory myasthenia gravis (MG)?

24. Is alpha-synuclein a useful target for Parkinson’s disease (PD) treatment?

25. Are monoclonal antibodies to CGRP or its receptor effective and safe in migraine?

26. Is EEG usually necessary when diagnosing epilepsy?

27. Should patients with medication overuse headache be treated only after analgesic withdrawal?

28. Are monoclonal antibodies superior to immunotherapies for myasthenia gravis (MG)?

29. Should all patients with CIDP be tested for autoantibodies to nodal proteins?

30. Are non-epileptic seizures really psychogenic?

 

Southern Chivalry: Argument Vs Clubs. elycefeliz on Flikr. https://www.flickr.com/photos/elycefeliz/6271932825

 

CONy is reassurance for the jobbing neurologists, when they struggle to decide which guidance to follow and which to dismiss, that they can blame it all on the unanswered questions of neurology. Going through this list of controversies, it is comforting that the experts differ in their answers to these questions. The acknowledgement of uncertainty allows novices to avoid searching for non-existent black and white answers. It is also confirmation that even established assumptions are not unshakable.

***

Below are links to all 15 CONy conferences and their key controversies:

1st CONy 2007: Berlin, Germany

  • Should clinically isolated syndromes (CIS) be treated?
  • Is stem cell therapy an imminent treatment in advanced multiple sclerosis (MS)?
  • Is vascular cognitive impairment a misleading concept?
  • Is mild cognitive impairment a misleading concept?

2nd CONy 2008: Athens, Greece

  • Can physical trauma precipitate multiple sclerosis?
  • Should patients with Parkinson’s disease (PD) be treated in the pre-motor phase?
  • What is the first line therapy for chronic inflammatory demyelinating polyneuropathy (CIDP)?
  • Is intravenous immunoglobulin (IVIg) effective in chronic myasthenia gravis (MG)?
  • Tau or ß-amyloid immunotherapy in Alzheimer’s disease (AD)?
  • Is chronic fatigue syndrome an organic disease and should it be treated by neurologists?

3rd CONy 2009: Prague, Czech Republic

  • Should cerebrospinal fluid (CSF) be tested in every clinically isolated syndrome?
  • Can we prevent multiple sclerosis (MS) by early vitamin D supplementation and EBV vaccination?
  • Does Parkinson’s disease (PD) have a prion-like pathogenesis?
  • Should patients with medication overuse headache be treated only after analgesic withdrawal?

4th CONy 2010: Barcelona, Spain

  • Is camptocormia in Parkinson’s disease (PD) a dystonia or a myopathy?
  • Does chronic venous insufficiency play a role in the pathogenesis of multiple sclerosis (MS)?
  • Is IVIg better than immunosuppression for long-term treatment of chronic inflammatory demyelinating polyneuropathy (CIDP)?

5th CONy 2011: Beijing, China

  • Is sporadic Parkinson’s disease aetiology predominantly environmental or genetic?
  • Is multiple sclerosis (MS) an inflammatory or a primarily neurodegenerative disease?
  • Are the new multiple sclerosis oral medications superior to conventional therapies?
  • Is bilateral transverse venous sinus stenosis a critical finding in idiopathic intracranial hypertension (IIH)?

6th CONy 2012: Vienna, Austria

  • Will there ever be a valid biomarker for Alzheimer’s disease (AD)?
  • Is amyloid imaging clinically useful in Alzheimer’s disease (AD)?
  • Do functional syndromes have a neurological substrate?
  • Should blood pressure be lowered immediately after stroke?
  • Is migraine is primarily a vascular disorder?

7th CONy 2013: Istanbul, Turkey

  • Is intravenous thrombolysis the definitive treatment for acute large artery stroke?
  • Should atrial fibrillation related stroke be treated only with the new anticoagulants?
  • Is the best treatment for chronic migraine botulinum toxin?
  • IS CGRP the key molecule in migraine?
  • Is chronic cluster headache best treated with sphenopalatine ganglion (SPG) stimulation?
  • When should deep brain stimulation (DBS) be initiated for Parkinson’s disease?
  • Do interferons prevent secondary progressive multiple sclerosis (SPMS)?
  • Is deep brain stimulation (DBS) better than botulinum toxin in primary dystonia?
  • Should radiologically isolated syndromes (RIS) be treated?
  • Does genetic testing have a role in epilepsy management?
  • Should cortical strokes be treated prophylactically against seizures?
  • Should enzyme-inducing anti-epileptic drugs (AEDs) be avoided?
  • Is EEG usually necessary when diagnosing epilepsy?

8th CONy 2014: Berlin, Germany

  • Is late-onset depression prodromal neurodegeneration?
  • Does Parkinson’s disease begin in the peripheral nervous system?
  • What is the best treatment in advanced Parkinson’s disease?
  • Are most cryptogenic epilepsies immune mediated?
  • Should epilepsy be diagnosed after the first unprovoked seizure?
  • Do anti-epileptic drugs (AEDs) contribute to suicide risk?
  • Should the ketogenic diet be prescribed in adults with epilepsy?
  • Do patients with idiopathic generalised epilepsy require lifelong treatment?

9th CONy 2015: Budapest, Hungary

  • Is discontinuation of disease-modifying therapies safe in long-term stable multiple sclerosis?
  • Is behavioral therapy necessary for the treatment of migraine?
  • Which is the first-line therapy in cases of IIH with bilateral papilledema?
  • Should patients with unruptured arterio-venous malformations (AVM) be referred for intervention?
  • Should survivors of hemorrhagic strokes be restarted on oral anticoagulants?
  • Will stem cell therapy become important in stroke rehabilitation?
  • Do statins cause cognitive impairment?

10th CONy 2016: Lisbon, Portugal

  • Which should be the first-line therapy for CIDP? Steroids vs. IVIg
  • Should disease-modifying treatment be changed if only imaging findings worsen in multiple sclerosis?
  • Should disease-modifying therapies be stopped when secondary progressive MS develops?
  • Should non-convulsive status epilepsy be treated aggressively?
  • Does traumatic chronic encephalopathy (CTE) exist?
  • Does corticobasal degeneration (CBD) exist as a clinico-pathological entity?
  • Is ß-amyloid still a relevant target in AD therapy?
  • Will electrical stimulation replace medications for the treatment of cluster headache?
  • Should anticoagulants be used to treat carotid  artery dissection?
  • Is the ABCD2 grading useful for clinical management of TIA patients?
  • Do COMT inhibitors have a future in treatment of Parkinson’s disease?

11th CONy 2017: Athens, Greece

  • Is suspected non-amyloid pathology (SNAP) a preclinical state of Alzheimer’s disease (AD)?
  • Does cognitive reserve prevent neurodegeneration?
  • Is mild cognitive impairment (MCI) a useful concept?
  • Should we give a diagnosis of epilepsy to someone who has had only one seizure?
  • Should anti-epileptic drugs be withdrawn after 2 years of seizure freedom?
  • Is neurodegeneration in multiple sclerosis (MS) always the consequence of inflammation?
  • Should thymectomy should be performed for all patients with myasthenia gravis?
  • Is alpha-synuclein a useful biomarker in Parkinson’s disease (PD)?
  • Should patients with embolic stroke of undetermined source (ESUS) be anticoagulated?
  • Is intravenous thrombolysis effective in wake-up stroke with normal baseline CT?
  • Should anticoagulation be restarted following anticoagulation-related intracerebral hemorrhage?

12th CONy 2018: Warsaw, Poland

  • Can the diagnosis of Alzheimer’s disease (AD) be made solely on biomarker evidence?
  • Do the clinical criteria of normal pressure hydrocephalus (NPH) predict response to shunting?
  • Is continuous EEG always required to reliably diagnose psychogenic seizures?
  • Is cerebrospinal fluid (CSF) examination necessary to diagnose multiple sclerosis (MS)?
  • Should multiple sclerosis (MS) treatment be stopped after 5 years of apparently inactive disease?
  • Is the aetiology of Parkinson’s disease (PD) predominantly genetic?
  • Is Parkinson’s disease (PD) a prion disease?
  • Is vagotomy protective against Parkinson’s disease (PD)?
  • Should patent foramen ovale (PFO) closure be a standard treatment for embolic stroke of undetermined source (ESUS)?

13th CONy 2019: Madrid, Spain

  • Is preclinical Alzheimer’s disease (AD) a useful term?
  • Will serum neurofilament light (NFL) levels replace MRI in monitoring multiple sclerosis (MS) progression?
  • Do evoked potentials (EPs) still have a role in multiple sclerosis (MS) diagnosis and monitoring?
  • Are non-epileptic seizures really psychogenic?
  • Does a high number of cerebral microbleeds (CMBs) contraindicate anticoagulant treatment?
  • Are direct acting oral anticoagulants (DOACs) better than anti-platelet medications in patients with embolic strokes of undetermined source (ESUS)?
  • Is the amyloid cascade the key etiological factor in Alzheimer’s disease (AD)?
  • Is herpes virus infection a risk factor for Alzheimer’s disease (AD)?
  • Is corticobasal degeneration (CBD) the same as progressive supranuclear palsy (PSP)?
  • Are microbiota reasonable targets in the therapy of neurodegenerative diseases?
  • Is heavy physical exercise a risk factor for amyotrophic lateral sclerosis (ALS)?

14th CONy 2020: Virtual

  • Should immunoglobulins or steroids be used first in the treatment of chronic inflammatory demyelinating polyradiculopathy (CIDP)?
  • Is CSF alpha-synuclein a useful biomarker for Parkinson’s disease (PD)?
  • Are β-amyloid and tau wrong treatment targets in sporadic, late onset Alzheimer’s disease (AD)?
  • Does vestibular migraine exist?
  • Should combination antiepileptic drugs (AED) be used immediately after failure of a singleAED?
  • Should antithrombotic therapy be avoided in the presence of cerebral microbleeds (CMBs)?
  • Do diffusion weighted imaging (DWI) negative strokes exist?
  • Should newly diagnosed multiple sclerosis (MS) be started on aggressive therapy?
  • Is cognitive reserve just a buzzword lacking scientific value?
  • Do infectious agents trigger and influence neurodegeneration?

15th CONy 2021: Virtual

  • Is alpha-synuclein (α-syn) a useful target for Parkinson’s disease (PD) treatment?
  • Are monoclonal antibodies to CGRP or its receptor effective and safe in migraine?
  • Should serum neurofilament light (NfL) replace brain MRI in monitoring multiple sclerosis (MS) disease activity?
  • Should GLP1 agonists be part of the treatment in stroke prevention in patients with diabetes?
  • Is CT perfusion sufficient for thrombolysis decision making in wake-up strokes?
  • Are monoclonal antibodies superior to immunotherapies for myasthenia gravis (MG)?
  • Should all patients with chronic inflammatory demyelinating polyneuropathy (CIDP) be tested for autoantibodies to nodal proteins?
  • Should anti-epileptic drugs (AEDs) be routinely prescribed for prophylaxis in people with brain tumours?

***

Do you have the definitive answers to resolve these controversies? Are there important controversies that are missing here? Please leave a comment

 

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s