Ophthalmological signs and sensorimotor evaluation in mitochondrial diseases: a multidisciplinary prospective study DOI Creative Commons
Gustavo Savino, Federico Giannuzzi, Valentina Cima

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 3, 2023

Abstract Background. Primary mitochondrial myopathies (PMM) are disorders that involve defects in oxidative phosphorylation (OXPHOS) and impair mainly, but not exclusively, skeletal muscles. Progressive external ophthalmoplegia (PEO), eyelid ptosis, exercise intolerance muscle weakness the most common symptoms of myopathy diseases, impairing ocular motility visual abilities. Methods. Twenty-five patients underwent complete ophthalmological examination, including best corrected acuity (BCVA), ptosis evaluation, dilated fundus orthoptic examinations, cover cover-uncover test, analysis, fusional amplitude (FA) vergence for near distance, Bagolini striated glasses test (BSGs) Worth four-dot lights (WFDT). Results. Mean age at evaluation was 47,2±16.07 years. Twenty-two (88%) out 25 had a PEO disease, while three (12%) them Kearn-Sayre syndrome (KSS). Ocular impairment found 92% population. Fifteen (60%) didn’t complain double vision casual seeing condition despite some showed manifest strabismus both far (53%) (60%). A compensation sensorial mechanism, mainly suppression, detected through sensory tests. The distance capabilities convergence divergence (CFAs DFAs) were absent 68 72% whole sample respectively. manifests an older than KSS (p=0.003), diplopia does correlate with disease duration (p=0.06) no predictive factors can be identified. Conclusions. significant number complaining state or latent/manifest FAoD NAoD. Most strabismic monocular suppression alternate tests (BSGs WFDT). pathophysiology these adaptations adult system only hypothesized. multidisciplinary approach is essential proper clinical management to analyze understand features pathogenesis.

Language: Английский

Delineating mechanisms underlying parvalbumin neuron impairment in different neurological and neurodegenerative disorders: the emerging role of mitochondrial dysfunction DOI Creative Commons
Elizaveta A. Olkhova, Laura A. Smith,

Bethany H. Dennis

et al.

Biochemical Society Transactions, Journal Year: 2024, Volume and Issue: 52(2), P. 553 - 565

Published: April 2, 2024

Given the current paucity of effective treatments in many neurological disorders, delineating pathophysiological mechanisms among major psychiatric and neurodegenerative diseases may fuel development novel, potent that target shared pathways. Recent evidence suggests various pathological processes, including bioenergetic failure mitochondria, can perturb function fast-spiking, parvalbumin-positive neurons (PV+). These inhibitory critically influence local circuit regulation, generation neuronal network oscillations complex brain functioning. Here, we survey PV+ cell vulnerability neuropsychiatric, review associated cellular molecular alterations purported to underlie disease aetiology.

Language: Английский

Citations

0
Deep Brain Stimulation for Medication Refractory Tremor in Leber Optic Neuropathy Plus Syndrome DOI Open Access

Gunjanpreet Kaur,

Yoan Ganev,

Wilson Rodriguez

et al.

Cureus, Journal Year: 2024, Volume and Issue: unknown

Published: April 14, 2024

Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder that presents with acute to subacute onset of unilateral progressive neuropathy, sequential involvement the fellow eye months years later. The condition may be accompanied by neurological symptoms, including tremors, dystonia, seizures, or psychosis, in which case, it termed LHON-plus. Here, we present case 53-year-old man who was initially diagnosed essential tremor but later found have LHON-plus after bilateral visual loss and genetic panel. His refractory standard pharmacological therapies, propranolol, primidone, topiramate. As result, he elected undergo deep brain stimulation (DBS) ventral intermediate nucleus thalamus dramatic improvement symptoms. To our knowledge, this first presenting context treated successfully DBS. While DBS has been applied dystonia limited success, outcome suggests there promise approach more research needed evaluate it.

Language: Английский

Citations

0
Movement disorders associated with neuromuscular and mitochondrial disorders DOI
Jinyoung Youn, Woo Young Jang, Eungseok Oh

et al.

International review of movement disorders, Journal Year: 2024, Volume and Issue: unknown, P. 63 - 101

Published: Jan. 1, 2024

Language: Английский

Citations

0
Peripheral nerve injury induces dystonia-like movements and dysregulation in the energy metabolism: A multi-omics descriptive study in Thap1+/− mice DOI Creative Commons

Colette Reinhold,

Susanne Knörr, Rhonda L. McFleder

et al.

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: unknown, P. 106783 - 106783

Published: Dec. 1, 2024

DYT-THAP1 dystonia is a monogenetic form of dystonia, movement disorder characterized by the involuntary co-contraction agonistic and antagonistic muscles. The disease caused mutations in THAP1 gene, although precise mechanisms which these contribute to pathophysiology remain unclear. incomplete penetrance estimated at 40 60 %, suggests that an environmental trigger may be required for manifestation genetically predisposed individuals. To investigate gene-environment interaction development dystonic features, we performed sciatic nerve crush injury heterozygous knockout mouse model (Thap1

Language: Английский

Citations

0
Mitochondrial disease in neurology—Past, present, and future DOI
Patrick F. Chinnery

Handbook of clinical neurology, Journal Year: 2023, Volume and Issue: unknown, P. 3 - 6

Published: Jan. 1, 2023

Language: Английский

Citations

1
Neurological Phenotypes in Mouse Models of Mitochondrial Disease and Relevance to Human Neuropathology DOI Open Access
Elizaveta A. Olkhova, Laura A. Smith,

Carla Bradshaw

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(11), P. 9698 - 9698

Published: June 2, 2023

Mitochondrial diseases represent the most common inherited neurometabolic disorders, for which no effective therapy currently exists patients. The unmet clinical need requires a more comprehensive understanding of disease mechanisms and development reliable robust in vivo models that accurately recapitulate human disease. This review aims to summarise discuss various mouse harbouring transgenic impairments genes regulate mitochondrial function, specifically their neurological phenotype neuropathological features. Ataxia secondary cerebellar impairment is one prevalent features dysfunction, consistent with observation progressive ataxia manifestation patients loss Purkinje neurons shared finding post-mortem tissues numerous models. However, none existing other devastating phenotypes, such as refractory focal seizures stroke-like episodes seen Additionally, we roles reactive astrogliosis microglial reactivity, may be driving neuropathology some well through cellular death occur, beyond apoptosis, undergoing bioenergy crisis.

Language: Английский

Citations

1
Effective treatment of choreaballism due to an MT‐CYB variant with haloperidol, tetrabenazine, and antioxidants DOI Creative Commons
Josef Finsterer, Ritwik Ghosh

Clinical Case Reports, Journal Year: 2023, Volume and Issue: 11(6)

Published: June 1, 2023

Hypokinetic and hyperkinetic movement disorders are a common phenotypic feature of mitochondrial disorders. Choreaballism has been reported particularly in patients with encephalopathy, lactic acidosis, stroke-like episodes syndrome maternally inherited diabetes deafness syndrome. The pathophysiological basis is the involvement basal ganglia or midbrain. Haloperidol cocktails have proven beneficial some these cases. Here we present another patient choreaballism who benefited significantly from symptomatic therapy. 14-year-old male history hypoacusis, ptosis, focal tonic-clonic seizures upper/lower limbs on either side since childhood. Since this time he also developed occasional, abnormal involuntary limb movements, choreaballism, facial grimacing, carpopedal spasms, lip sensations. He was diagnosed non-syndromic disorder after detection variant m.15043G > A

Language: Английский

Citations

1
Ophthalmological signs and sensorimotor evaluation in mitochondrial diseases: a multidisciplinary prospective study DOI Creative Commons
Gustavo Savino, Federico Giannuzzi, Valentina Cima

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 3, 2023

Abstract Background. Primary mitochondrial myopathies (PMM) are disorders that involve defects in oxidative phosphorylation (OXPHOS) and impair mainly, but not exclusively, skeletal muscles. Progressive external ophthalmoplegia (PEO), eyelid ptosis, exercise intolerance muscle weakness the most common symptoms of myopathy diseases, impairing ocular motility visual abilities. Methods. Twenty-five patients underwent complete ophthalmological examination, including best corrected acuity (BCVA), ptosis evaluation, dilated fundus orthoptic examinations, cover cover-uncover test, analysis, fusional amplitude (FA) vergence for near distance, Bagolini striated glasses test (BSGs) Worth four-dot lights (WFDT). Results. Mean age at evaluation was 47,2±16.07 years. Twenty-two (88%) out 25 had a PEO disease, while three (12%) them Kearn-Sayre syndrome (KSS). Ocular impairment found 92% population. Fifteen (60%) didn’t complain double vision casual seeing condition despite some showed manifest strabismus both far (53%) (60%). A compensation sensorial mechanism, mainly suppression, detected through sensory tests. The distance capabilities convergence divergence (CFAs DFAs) were absent 68 72% whole sample respectively. manifests an older than KSS (p=0.003), diplopia does correlate with disease duration (p=0.06) no predictive factors can be identified. Conclusions. significant number complaining state or latent/manifest FAoD NAoD. Most strabismic monocular suppression alternate tests (BSGs WFDT). pathophysiology these adaptations adult system only hypothesized. multidisciplinary approach is essential proper clinical management to analyze understand features pathogenesis.

Language: Английский

Citations

0