Pearls & Oysters: Paroxysmal Exercise-Induced Dyskinesias Due to Pyruvate Dehydrogenase Deficiency 2023 de Gusmao et al

[Andy]

Abstract

Paroxysmal exercise-induced movement disorders may be caused by energy metabolism disorders, such as Glut 1 deficiency, pyruvate dehydrogenase deficiency or mitochondrial respiratory chain disorders. A 4-year-old boy with a history of febrile seizures presented with paroxysmal dystonia, triggered by exercise, or occurring at rest. Additional investigations demonstrated pallidal hyperintensities on brain MRI and low CSF glucose. Pyruvate and lactate were elevated. The clinical presentation, combined with neuroimaging abnormalities and biochemical profile (the lactate/pyruvate ratio) were clues to pyruvate dehydrogenase deficiency, a treatable metabolic disorder with neurological presentations.

Open access, https://n.neurology.org/content/early/2023/02/20/WNL.0000000000207142

 

[Hutan]

I read this account and get a sense of what a difference a good clinical team and a decent set of tests can make as to whether someone has a lifetime of unexplained medical issues (or worse, a functional diagnosis) or they get a diagnosis that leads to understanding and helpful treatment. I mean, I would hope someone would get properly diagnosed but I'm sure there are many parts of the world where they do not.

In his second year of life, he developed an upper extremity postural tremor and had three uncomplicated febrile seizures. Initial investigations including EEG, basic laboratory and neuroimaging were non-diagnostic, and he was not treated.

At age 4, he presented with episodes of gait difficulty, manifested by “turning in” of one or both feet, sometimes with imbalance. The episodes would occur daily and could last several minutes. The most consistent trigger was exercise (e.g., walking a mile to school), but they could also occur in the setting of fatigue, after meals or without a clear reason. (Video 1) Occasionally, he voiced an ill-defined prodromal sensation that heralded an episode. Carbamazepine was tried empirically but was unhelpful and worsened his tremor.

Medication resistant symptoms, associated with walking to school - BPS heaven.

Just putting this here, as a differential diagnosis for ME/CFS. Of course it's different, but there was also fatigue and the association with exercise, so it might be confused with ME/CFS and certainly it might be confused with some sort of chronic fatigue/functional movement disorder thing.

Paroxysmal Exercise-induced Dyskinesia

PED is a genetic heterogeneous condition characterized by recurrent episodes of sudden, involuntary movements induced by prolonged exercise. 1 Patients may present with variable combinations of dystonia and/or chorea, most notably in the limbs involved with the exercise. 2 The exact amount of exercise necessary to induce an attack is not well defined. Typical attack duration may range from 5-30 minutes, however, this can be quite variable.3

There's a genetic cause.

 

[SNT Gatchaman]

High fives all round that team. For interest, the FLAIR hyperintensity in the globi pallidi is non-specific and can be seen in a number of metabolic conditions and toxin exposures. Classically carbon monoxide affects those same parts of the basal ganglia symmetrically, while methanol tends to affect the putamina, which are just outside the bright arrowed bits shown in this case.



These sorts of mitochondrial disorders can cause lots of damaging effects in the brain and there are quite a number of different types. MRIs try to give a steer to the metabolic neurologists based on the pattern of brain involvement. This is sometimes helpful for the geneticists when targeting the likely candidates.

This case is an example of the sorts of conditions that Jo's colleague would be seeing that is so different to the reversible/non-destructive type picture in ME/CFS, where MRIs look "within normal limits" based on our current understanding*.

I just don't see PWME as having the sort of problem I have been used to seeing in people with heart failure or other organ system failure where ATP mediated energy supply is limited.
[...]
I may be wrong but this is a view strongly endorsed by a colleague who works full time with people with mitochondrial disease. He said the picture was quite different.

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*"Normal" findings of perivascular spaces and choroid plexus calcification may turn out to be more important than we've given them credit for. Further studies pending.

 

[Mithriel]

I have paroxysmal dyskinesia and over the years there have been a few other ME patients who have said it is part of their disease. Official descriptions say that some patients while identical in presentation have a psychologically induced version which is diagnosed by taking a holistic view of the patient so guess what my neurologist said. Out the door, abandoned. Though one doctor asked how long I had had choreoathetosis so that is as close as I have got to empathy.

I became friendly with an MS sufferer who had the same problem and it was a relief to be able to talk to her and joke about things like giving my husband a black eye and having little kids wave back!

She was told that people can have a mild inherited problem but a major neurological disease makes it worse, though that was about 20 years ago so thinking may have changed

It is embarrassing and exhausting. Looking at descriptions I have the kinesegenic form mostly with some nonkinesegenic episodes but the worst symptoms are usually after too much exertion. Baclofen and gabapentin tone down the movements a bit and my GP is willing to prescribe them.

Recently came across a paper about cases being caused by a reactivation of HHV6 which could provide a link to ME.

I have so many of these weird symptoms it annoys me that fatigue is all that is taken into account especially when other things are so disabling and may give clues to how ME works.