Benedetta Storti1,2, Camillo Foresti2, Roberto Donati 3
1 Department of Neurology, Milano Bicocca, Italy
2 UOS Neurophysiology, UOC Neurology ASST Papa Giovanni XXIII, Bergamo, Italy
3 UOC Neurosurgery ASST Papa Giovanni XXIII, Bergamo, Italy
Dystonia associated with DYT1 mutation is an early-onset isolated dystonia usually first apparent with focal symptoms. Over time, the contractions spread to other body regions and become evident and debilitating. However, disease severity varies considerably even within the same family and isolated writer’s cramp may be the only sign. Emma is a brave girl affected by a severe form of DYT1 Dystonia who underwent deep brain stimulation (DBS) implant in March 2021. She has taught me a lesson of courage and determination I would like to share.
At the very starting point of the novel “Emma”, Jane Austen reveals to the readers: “I am going to take a heroine whom no one but myself will much like”. Accordingly, or, better to say, dis-accordingly, in this letter I would tell the story of another Emma, whom everyone will much like. Emma Woodhouse, in the novel, “had lived nearly twenty-one years in the world with very little to distress or vex her”; contrarily, Emma R., who was twenty-two when I first met her, had left behind normality when she was thirteen. Indeed, Emma R. was diagnosed with DYT-1 dystonia at that age. When she was attending the third year of secondary school, she progressively developed difficulties in writing with her right hand: it writhed involuntarily and caused the pencil to fall down. She was forced to write with her left hand and she became left-handed with much practice and many troubles; until the spared hand turned to be dystonic too.
As years went by, the muscles abnormal contractions spread to her right leg and she had to give up horse riding at about sixteen. In spite of the disturbing movement disorder, Emma R. finished her study, got engaged to a solid boy and found a job as a secretary in a private office. Even though she was widely affected by torsion dystonia, it was difficult to notice that at first glance. She had developed several different tricks that reduced the dystonic symptoms: one of these was placing her right foot behind the left one while sitting. Nevertheless, dystonia was always lying in wait, and it was sufficient to sit by her at lunch to observe the exhausting battle against the knife and the fork she was fighting. When Emma first developed the symptoms, they were not a surprise. In fact, when she was eight, all paternal relatives had undergone genetic screening because of an early-onset dystonia in a father’s aunt. Emma’s father had pathogenic TOR1A three base-pair deletion (c.907_909 GAG), and so did Emma. However, he was totally asymptomatic, Emma was not. DYT1 dystonia is an autosomal dominant pathology with penetrance of about 30% (1). As follows, the child of a mutation carrier has a change of 50% of inheriting the variant and, if inherited, a 30% chance of developing symptoms. Emma had a 15% chance of winning this lottery and, unfortunately, she did.
With the spreading of the symptoms, Emma started to suffer continuous pain and cramping due to involuntary muscle movements. She was visited by several different movement disorder specialists and she tried most of the available treatments to treat dystonia (trihexyphenidyl, baclofen, benzodiazepines, tetrabenazine) (2). Every drug was quite ineffective. According to the DYT1 pathology, a trial of dopamine medication, rather useful in Segawa syndrome, was not performed (3). Emma had first-hand experience of many adverse effects and felt partial relief only with botulinum toxin injections and off-label oral preparations containing ∆9-tetrahydrocannabinol (4).
Emma came to our hospital the first time when she was twenty-two. Involuntary intermittent contraction of muscles involved the four limbs and were present also at rest. She had a multifocal dystonia, with the trunk being spared. A surgical approach was proposed and after months of thoughtful reflection Emma agreed.
The deep brain stimulation (DBS) implant (Activa RC, Medtronic Inc.) was performed in March 2021 and Emma underwent it under local anaesthesia: she was totally awake and actively participating in neurostimulator placement. At a certain point, when the left electrode was approaching the target on the globus pallidus and she was asked to open and close her right hand quickly, she emotionally said: I haven’t been able to do this movement for the last 10 years and now I can.
Emma was lucky. Even though the DBS surgery was scheduled months in advance, there was a high risk it would be cancelled due to the COVID-19 emergency: in March, half of the elective surgical activity in our hospital was postponed due to the third wave of the pandemic.
Only a few months after the procedure Emma is making great progress. She is relearning how to use her right hand and she is dreaming of buying a pair of high heels shoes.
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Kamm C. Early onset torsion dystonia (Oppenheim’s dystonia). Orphanet J Rare Dis. 2006 Nov 27;1:48. doi: 10.1186/1750-1172-1-48. PMID: 17129379; PMCID: PMC1693547.
Wijemanne S, Jankovic J. Dopa-responsive dystonia–clinical and genetic heterogeneity. Nat Rev Neurol. 2015 Jul;11(7):414-24. doi: 10.1038/nrneurol.2015.86. Epub 2015 Jun 23. PMID: 26100751.
Kluger B, Triolo P, Jones W, Jankovic J. The therapeutic potential of cannabinoids for movement disorders. Mov Disord. 2015 Mar;30(3):313-27. doi: 10.1002/mds.26142. Epub 2015 Feb 4. PMID: 25649017; PMCID: PMC4357541.
Financial Disclosures: The authors declare no disclosures.
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