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Page 232 Musumeci et al. J Transl Genet Genom 2020;4:221-37 I https://doi.org/10.20517/jtgg.2020.22

Levodopa and oral baclofen are the most common reported medications to treat dystonia, both drugs being
well tolerated but the efficacy is variable. Treatments with intrathecal baclofen or deep brain stimulation are
not yet reported in the literature [120] .

Botulinum neurotoxin injections are useful to treat focal or multifocal dystonia. Other medications such as
oral baclofen, tizanidine, or trihexyphenidyl have been reported in few patients and data on their efficacy are
[8]
inconsistent . A positive response for myoclonus may be seen with levetiracetam, clonazepam, or valproate,
although for the latter particular attention should be paid in patients with MD because of its possible
toxicity [121] .

MP patients benefit from dopaminergic treatment, although few cases have not had an optimal response to
L-DOPA and early onset dyskinesia has also been reported. It is evidenced that symmetrical nigrostriatal
[14]
degeneration at DAT-SCAN predicts a better response to treatment .
From a perspective point of view, several attempts have been made to counteract mitochondrial dysfunctions.
Many compounds active in mitochondrial biogenesis by activation of the pathway peroxisome proliferator-
activated receptor γ, as well as its coactivator 1a (PGC1a), have been tested in patients with PD but most of
them fail to produce a real benefit. Among them, some antidiabetic drugs acting on these mechanisms, such
as pioglitazone and exenatide, have been tested in preclinical studies as well as clinical trials on PD patients,
[88]
but their efficacy is uncertain .

Preclinical studies have shown benefit to boosting mitochondrial function but translation in humans is still
far from being a reality.

CONCLUSION
Movement disorders are part of the clinical spectrum of MD among both pediatric and adult patients
usually in the context of a mitochondrial multisystem presentation. Data on the true incidence of MoD
are quite limited because no population-based studies are available. In children, dystonia and ataxia
are the most common MoD, more frequently associated with mtDNA mutations. In adults, myoclonus,
ataxia, and parkinsonism are reported either in mtDNA mutations syndromes or in nDNA mutations,
causing alterations of mtDNA maintenance. Basal ganglia and cerebellum degeneration appear to be the
neuropathological substrate of MoD but the pathological mechanisms need still to be clarified. “Mitochondrial
parkinsonism” is an emerging topic and should be suspected in patients manifesting an akinetic syndrome
with PEO and myopathic signs. Treatment of these disorders is largely empirical and large cohort studies are
necessary to improve the management of MD patients with MoD.

DECLARATIONS
Authors’ contributions
Made substantial contributions to conception and design of the study and performed data analysis and
interpretation: Musumeci O, Toscano A
Performed data acquisition, technical, and material support: Oteri R

Availability of data and materials
Not applicable.

Financial support and sponsorship
This work was supported by Telethon (GUP9004, GSP16001)