Bilateral horizontal gaze palsy in an 8-year-old girl; a rare case with NDUFS4 gene mutation: a case report and literature review

Abstract Background: Leigh syndrome (LS) is a rare and inherited disease which is associated with progressive neurological disorders. The molecular underlying mechanism in LS is defined with some defects in mitochondrial respiratory chain enzymes. Case presentation: Here, an 8-year-old girl is reported with bilateral horizontal gaze palsy, ataxia and drowsiness. She developed unsteady gait, drowsiness, progressive ataxia and intention tremor during her admission period. The laboratory tests were reported within normal values including biochemical, hematological, immunological, infectious and inflammatory markers and blood and cerebrospinal fluid (CSF) lactate. Brain magnetic resonance imaging (MRI) demonstrated dorsal midbrain, bilateral putamen nuclei and cerebellar dentate nucleus involvement. Ocular examination revealed retinal atrophy and pale disk in both sides. These symptoms were in favor of a neurodegenerative disorder. Magnetic resonance spectroscopy (MRS) revealed an elevated lactate peak in involved areas which suggested a mitochondrial disease. Finally, the molecular genetic test reported NDUFS4 gene mutation which confirmed the presence of Leigh syndrome. She responded significantly to mitochondrial treatment cocktail and clinical signs and symptoms improved gradually. NDFUS4 gene encodes a subunit of mitochondrial complex I (NADH: ubiquinone oxidoreductase) that removes electrons from NADH and transfers them to the electron acceptor ubiquinone. Conclusion: Our findings indicated that various symptoms and clinical features can be found in Leigh syndrome which could be probably due to different mutations in mitochondrial genes. Therefore, appropriate clinical and laboratory settings along with brain MRI, MRS and genetic test analysis would be necessary for the early diagnosis.

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Imaging the Pathophysiology of Essential Tremor—A Systematic Review

Frontiers in Neurology ◽

10.3389/fneur.2021.680254 ◽

2021 ◽

Vol 12 ◽

Author(s):

Florian Holtbernd ◽

N. Jon Shah

Keyword(s):

Magnetic Resonance ◽

Essential Tremor ◽

Neurodegenerative Disorder ◽

Aminobutyric Acid ◽

Emission Computed Tomography ◽

Resonance Spectroscopy ◽

Gamma Aminobutyric Acid ◽

Imaging Studies ◽

Limited Evidence ◽

Neurotransmitter System

Background: The pathophysiology underlying essential tremor (ET) still is poorly understood. Recent research suggests a pivotal role of the cerebellum in tremor genesis, and an ongoing controversy remains as to whether ET constitutes a neurodegenerative disorder. In addition, mounting evidence indicates that alterations in the gamma-aminobutyric acid neurotransmitter system are involved in ET pathophysiology. Here, we systematically review structural, functional, and metabolic neuroimaging studies and discuss current concepts of ET pathophysiology from an imaging perspective.Methods: We conducted a PubMed and Scopus search from 1966 up to December 2020, entering essential tremor in combination with any of the following search terms and their corresponding abbreviations: positron emission tomography (PET), single-photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and gamma-aminobutyric acid (GABA).Results: Altered functional connectivity in the cerebellum and cerebello-thalamico-cortical circuitry is a prevalent finding in functional imaging studies. Reports from structural imaging studies are less consistent, and there is no clear evidence for cerebellar neurodegeneration. However, diffusion tensor imaging robustly points toward microstructural cerebellar changes. Radiotracer imaging suggests that the dopaminergic axis is largely preserved in ET. Similarly, measurements of nigral iron content and neuromelanin are unremarkable in most studies; this is in contrast to Parkinson's disease (PD). PET and MRS studies provide limited evidence for cerebellar and thalamic GABAergic dysfunction.Conclusions: There is robust evidence indicating that the cerebellum plays a key role within a multiple oscillator tremor network which underlies tremor genesis. However, whether cerebellar dysfunction relies on a neurodegenerative process remains unclear. Dopaminergic and iron imaging do not suggest a substantial overlap of ET with PD pathophysiology. There is limited evidence for alterations of the GABAergic neurotransmitter system in ET. The clinical, demographical, and genetic heterogeneity of ET translates into neuroimaging and likely explains the various inconsistencies reported.

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PP05.7 – 2639: Horizontal gaze palsy with progressive scoliosis (HGPPS): The role of brain MRI and diffusion tensor imaging in diagnosis

European Journal of Paediatric Neurology ◽

10.1016/s1090-3798(15)30156-2 ◽

2015 ◽

Vol 19 ◽

pp. S48

Author(s):

G. Haliloglu ◽

C. Gunbey ◽

E. Serdaroglu ◽

K. Karlı Oguz

Keyword(s):

Diffusion Tensor Imaging ◽

Diffusion Tensor ◽

Brain Mri ◽

Progressive Scoliosis ◽

Horizontal Gaze ◽

And Diffusion ◽

Gaze Palsy

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Magnetic Resonance Spectroscopy in the Diagnosis of Dementia with Lewy Bodies

BioMed Research International ◽

10.1155/2014/809503 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Radoslaw Magierski ◽

Tomasz Sobow

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Magnetic Resonance ◽

Magnetic Resonance Spectroscopy ◽

Dementia With Lewy Bodies ◽

Clinical Symptoms ◽

Clinical Signs ◽

Lewy Bodies ◽

Resonance Spectroscopy ◽

Diagnosis Of Dementia

Dementia with Lewy bodies (DLB) is considered to be the second most frequent primary degenerative dementing illness after Alzheimer’s disease (AD). DLB, together with Parkinson’s disease (PD), Parkinson’s disease with dementia (PDD) belong toα-synucleinopathies—a group of neurodegenerative diseases associated with pathological accumulation of theα-synuclein protein. Dementia due to PD and DLB shares clinical symptoms and neuropsychological profiles. Moreover, the core features and additional clinical signs and symptoms for these two very similar diseases are largely the same. Neuroimaging seems to be a promising method in differential diagnosis of dementia studies. The development of imaging methods or other objective measures to supplement clinical criteria for DLB is needed and a method which would accurately facilitate diagnosis of DLB prior to death is still being searched. Proton magnetic resonance spectroscopy (1H-MRS) provides a noninvasive method of assessing anin vivobiochemistry of brain tissue. This review summarizes the main results obtained from the application of neuroimaging techniques in DLB cases focusing on1H-MRS.

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A Novel SUCLA2 Mutation Presenting as a Complex Childhood Movement Disorder

Journal of Child Neurology ◽

10.1177/0883073816666221 ◽

2016 ◽

Vol 32 (2) ◽

pp. 246-250 ◽

Cited By ~ 3

Author(s):

Caterina Garone ◽

Juliana Gurgel-Giannetti ◽

Simone Sanna-Cherchi ◽

Sindu Krishna ◽

Ali Naini ◽

...

Keyword(s):

Magnetic Resonance ◽

Movement Disorder ◽

Brain Mri ◽

Brain Magnetic Resonance Imaging ◽

Mitochondrial Respiratory Chain ◽

Resonance Spectroscopy ◽

Homozygous Mutation ◽

Psychomotor Delay ◽

Mtdna Depletion ◽

Magnetic Resonance Imaging Mri

SUCLA2 defects have been associated with mitochondrial DNA (mtDNA) depletion and the triad of hypotonia, dystonia/Leigh-like syndrome, and deafness. A 9-year-old Brazilian boy of consanguineous parents presented with psychomotor delay, deafness, myopathy, ataxia, and chorea. Despite the prominent movement disorder, brain magnetic resonance imaging (MRI) was normal while 1H-magnetic resonance spectroscopy (MRS) showed lactate peaks in the cerebral cortex and lateral ventricles. Decreased biochemical activities of mitochondrial respiratory chain enzymes containing mtDNA-encoded subunits and mtDNA depletion were observed in muscle and fibroblasts. A novel homozygous mutation in SUCLA2, the first one in the ligase coenzyme A (CoA) domain of the protein, was identified. Escalating doses of CoQ10 up to 2000 mg daily were associated with improvement of muscle weakness and stabilization of the disease course. The findings indicate the importance of screening for mitochondrial dysfunction in patients with complex movement disorders without brain MRI lesions and further investigation for potential secondary CoQ10 deficiency in patients with SUCLA2 mutations.

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Abnormalities of horizontal gaze. Clinical, oculographic and magnetic resonance imaging findings. II. Gaze palsy and internuclear ophthalmoplegia.

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp.53.3.200 ◽

1990 ◽

Vol 53 (3) ◽

pp. 200-207 ◽

Cited By ~ 60

Author(s):

A M Bronstein ◽

P Rudge ◽

M A Gresty ◽

G Du Boulay ◽

J Morris

Keyword(s):

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Internuclear Ophthalmoplegia ◽

Imaging Findings ◽

Resonance Imaging ◽

Horizontal Gaze ◽

Gaze Palsy

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Minipig Model of Huntington´s Disease: 1H Magnetic Resonance Spectroscopy of the Brain

Physiological Research ◽

10.33549/physiolres.932967 ◽

2016 ◽

pp. 155-163 ◽

Cited By ~ 4

Author(s):

M. JOZEFOVICOVA ◽

V. HERYNEK ◽

F. JIRU ◽

M. DEZORTOVA ◽

J. JUHASOVA ◽

...

Keyword(s):

White Matter ◽

Magnetic Resonance ◽

Neurodegenerative Disorder ◽

Resonance Spectroscopy ◽

1H Magnetic Resonance Spectroscopy ◽

Imaging Sequence ◽

Single Voxel ◽

Metabolite Concentrations ◽

Cognitive Disturbances ◽

The Brain

Huntington’s disease (HD) is an inherited autosomal neurodegenerative disorder affecting predominantly the brain, characterized by motor dysfunctions, behavioral and cognitive disturbances. The aim of this study was to determine changes in the brain of transgenic minipigs before HD onset using 1H magnetic resonance (MR) spectroscopy. Measurements were performed on a 3 T MR scanner using a single voxel spectroscopy sequence for spectra acquisition in the white matter and chemical shift imaging sequence for measurement in the striatum, hippocampus and thalamus. A decrease of (phospho)creatine (tCr) concentration was found only in the thalamus (p=0.002) of transgenic minipigs, nevertheless we found significant changes in metabolite ratios. Increase of the ratio choline compounds (tCho)/tCr was found in all examined areas: striatum (p=0.010), thalamus (p=0.011) as well as hippocampus (p=0.027). The ratio N-acetylaspartate+N-acetylaspartylglutamate (tNAA)/tCr (p=0.043) and glutamate+glutamine (Glx)/tCr (p=0.039) was elevated in the thalamus, the ratio myo-inositol (Ins)/tCr (p=0.048) was significantly increased in the hippocampus. No significant differences were observed in the metabolite concentrations in the white matter, however we found significant increase of ratios tNAA/tCr (p=0.018) and tCho/tCr (p=0.003) ratios in transgenic boars. We suppose that the majority of the observed changes are predominantly related to changes in energy metabolism caused by decrease of tCr.

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