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Neurology Jun 2024Degeneration of the presynaptic nigrostriatal dopaminergic system is one of the main biological features of Parkinson disease (PD), multiple system atrophy (MSA),...
BACKGROUND AND OBJECTIVES
Degeneration of the presynaptic nigrostriatal dopaminergic system is one of the main biological features of Parkinson disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), which can be measured using single-photon emission CT imaging for diagnostic purposes. Despite its widespread use in clinical practice and research, the diagnostic properties of presynaptic nigrostriatal dopaminergic (DAT) imaging in parkinsonism have never been evaluated against the diagnostic gold standard of neuropathology. The aim of this study was to evaluate the diagnostic parameters of DAT imaging compared with pathologic diagnosis in patients with parkinsonism.
METHODS
Retrospective cohort study of patients with DAT imaging for the investigation of a clinically uncertain parkinsonism with brain donation between 2010 and 2021 to the Queen Square Brain Bank (London). Patients with DAT imaging for investigation of pure ataxia or dementia syndromes without parkinsonism were excluded. Those with a pathologic diagnosis of PD, MSA, PSP, or CBD were considered presynaptic dopaminergic parkinsonism, and other pathologies were considered postsynaptic for the analysis. DAT imaging was performed in routine clinical practice and visually classified by hospital nuclear medicine specialists as normal or abnormal. The results were correlated with neuropathologic diagnosis to calculate diagnostic accuracy parameters for the diagnosis of presynaptic dopaminergic parkinsonism.
RESULTS
All of 47 patients with PD, 41 of 42 with MSA, 68 of 73 with PSP, and 6 of 10 with CBD (sensitivity 100%, 97.6%, 93.2%, and 60%, respectively) had abnormal presynaptic dopaminergic imaging. Eight of 17 patients with presumed postsynaptic parkinsonism had abnormal scans (specificity 52.9%).
DISCUSSION
DAT imaging has very high sensitivity and negative predictive value for the diagnosis of presynaptic dopaminergic parkinsonism, particularly for PD. However, patients with CBD, and to a lesser extent PSP (of various phenotypes) and MSA (with predominant ataxia), can show normal DAT imaging. A range of other neurodegenerative disorders may have abnormal DAT scans with low specificity in the differential diagnosis of parkinsonism. DAT imaging is a useful diagnostic tool in the differential diagnosis of parkinsonism, although clinicians should be aware of its diagnostic properties and limitations.
CLASSIFICATION OF EVIDENCE
This study provides Class II evidence that DAT imaging does not accurately distinguish between presynaptic dopaminergic parkinsonism and non-presynaptic dopaminergic parkinsonism.
Topics: Humans; Female; Aged; Male; Retrospective Studies; Dopamine Plasma Membrane Transport Proteins; Parkinsonian Disorders; Tomography, Emission-Computed, Single-Photon; Middle Aged; Multiple System Atrophy; Supranuclear Palsy, Progressive; Aged, 80 and over; Parkinson Disease; Cohort Studies; Corticobasal Degeneration; Dopamine; Presynaptic Terminals; Sensitivity and Specificity; Dopaminergic Imaging
PubMed: 38759132
DOI: 10.1212/WNL.0000000000209453 -
Medicine May 2024This study was aimed to analyze ocular biometric changes following cycloplegia in pediatric patients with strabismus and amblyopia. Cycloplegia is routinely used to... (Observational Study)
Observational Study
This study was aimed to analyze ocular biometric changes following cycloplegia in pediatric patients with strabismus and amblyopia. Cycloplegia is routinely used to measure refractive error accurately by paralyzing accommodation. However, effects on axial length (AL), anterior chamber depth (ACD), keratometry (Km), and white-to-white distance (WTW) are not well studied in this population. This retrospective study examined 797 patients (1566 eyes) undergoing cycloplegic refraction at a Samsung Kangbuk hospital pediatric ophthalmology clinic from 2010 to 2023. Ocular biometry was measured before and after instilling 1% cyclopentolate and 0.5% phenylephrine/0.5% tropicamide. Patients were categorized by strabismus diagnosis, age, refractive error and amblyopia status. Differences in AL, ACD, Km, WTW, and refractive error pre- and post-cycloplegia were analyzed using paired t tests. ACD (3.44 ± 0.33 vs 3.58 ± 0.29 mm, P < .05) and WTW (12.09 ± 0.42 vs 12.30 ± 0.60 mm, P < .05) increased significantly after cycloplegia in all groups except other strabismus subgroup (Cs) in both parameters and youngest subgroup (G1) in ACD. Refractive error demonstrated a hyperopic shift from -0.48 ± 3.00 D to -0.06 ± 3.32 D (P < .05) in overall and a myopic shift from -6.97 ± 4.27 to -8.10 ± 2.26 in high myopia (HM). Also, AL and Km did not change significantly. In conclusion, cycloplegia impacts ocular biometrics in children with strabismus and amblyopia, significantly increasing ACD and WTW. Refractive error shifts hyperopically in esotropia subgroup (ET) and myopically in high myopia subgroup (HM), eldest subgroup (G3) relating more to anterior segment changes than AL/Km. Understanding cycloplegic effects on biometry is important for optimizing refractive correction in these patients.
Topics: Humans; Amblyopia; Strabismus; Retrospective Studies; Male; Female; Child; Biometry; Mydriatics; Child, Preschool; Refraction, Ocular; Cyclopentolate; Refractive Errors; Adolescent; Anterior Chamber; Axial Length, Eye
PubMed: 38758890
DOI: 10.1097/MD.0000000000038143 -
The Medical Journal of Australia Jun 2024
Topics: Humans; Miller Fisher Syndrome; Botulism; Diagnosis, Differential; Brain Stem; Stroke; Male; Middle Aged; Female
PubMed: 38749924
DOI: 10.5694/mja2.52311 -
Brain and Nerve = Shinkei Kenkyu No... May 2024Fisher syndrome is recognized as a variant of Guillain-Barré syndrome, encompassing acute onset immune-mediated neuropathies marked by the classical triad of ataxia,... (Review)
Review
Fisher syndrome is recognized as a variant of Guillain-Barré syndrome, encompassing acute onset immune-mediated neuropathies marked by the classical triad of ataxia, areflexia, and ophthalmoplegia. Generally, Fisher syndrome follows a self-limited course with a good prognosis. Ophthalmoplegia, typically bilateral, progresses to complete external ophthalmoplegia within 1-2 weeks. Ataxia, often very severe, may cause an inability to walk without support despite normal strength. Fisher syndrome is also frequently concomitant with additional clinical features, including ptosis, internal ophthalmoplegia, facial nerve palsy, sensory deficits, and bulbar palsy. The confirmation of an antecedent infection is often established. Among the ganglioside antibodies, anti-GQ1b antibodies exhibit positivity in over 80% of patients. The syndrome manifests in three distinct types: a partial subtype exhibiting only a subset of the triad symptoms, Bickerstaff's brainstem encephalitis marked by impaired consciousness and pyramidal tract signs, and an overlapping subtype with Guillain-Barré syndrome, characterized by weakness in the extremities.
Topics: Humans; Miller Fisher Syndrome; Gangliosides; Prognosis; Guillain-Barre Syndrome
PubMed: 38741489
DOI: 10.11477/mf.1416202636 -
Journal of Neuro-ophthalmology : the... Jun 2024
Topics: Humans; Encephalitis, Varicella Zoster; Herpesvirus 3, Human; Magnetic Resonance Imaging; Ocular Motility Disorders; Video Recording
PubMed: 38741253
DOI: 10.1097/WNO.0000000000002026 -
Journal of Neuro-ophthalmology : the... Jun 2024
Topics: Humans; Ophthalmoplegia; Oculomotor Muscles; Autoantibodies; Female; Male; Middle Aged; Magnetic Resonance Imaging
PubMed: 38741251
DOI: 10.1097/WNO.0000000000001825 -
Journal of Translational Medicine May 2024Inherited deficiency of thymidine phosphorylase (TP), encoded by TYMP, leads to a rare disease with multiple mitochondrial DNA (mtDNA) abnormalities, mitochondrial...
Inherited deficiency of thymidine phosphorylase (TP), encoded by TYMP, leads to a rare disease with multiple mitochondrial DNA (mtDNA) abnormalities, mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). However, the impact of TP deficiency on lysosomes remains unclear, which are important for mitochondrial quality control and nucleic acid metabolism. Muscle biopsy tissue and skin fibroblasts from MNGIE patients, patients with m.3243 A > G mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) and healthy controls (HC) were collected to perform mitochondrial and lysosomal functional analyses. In addition to mtDNA abnormalities, compared to controls distinctively reduced expression of LAMP1 and increased mitochondrial content were detected in the muscle tissue of MNGIE patients. Skin fibroblasts from MNGIE patients showed decreased expression of LAMP2, lowered lysosomal acidity, reduced enzyme activity and impaired protein degradation ability. TYMP knockout or TP inhibition in cells can also induce the similar lysosomal dysfunction. Using lysosome immunoprecipitation (Lyso- IP), increased mitochondrial proteins, decreased vesicular proteins and V-ATPase enzymes, and accumulation of various nucleosides were detected in lysosomes with TP deficiency. Treatment of cells with high concentrations of dThd and dUrd also triggers lysosomal dysfunction and disruption of mitochondrial homeostasis. Therefore, the results provided evidence that TP deficiency leads to nucleoside accumulation in lysosomes and lysosomal dysfunction, revealing the widespread disruption of organelles underlying MNGIE.
Topics: Humans; Lysosomes; Thymidine Phosphorylase; Mitochondrial Encephalomyopathies; Fibroblasts; DNA, Mitochondrial; Mitochondria; Nucleosides; Intestinal Pseudo-Obstruction; Ophthalmoplegia; Muscular Dystrophy, Oculopharyngeal; Male; Female; Skin; Lysosomal-Associated Membrane Protein 2
PubMed: 38741129
DOI: 10.1186/s12967-024-05275-8 -
PeerJ 2024To track improvement in diplopia symptoms with strabismus-specific health-related quality of life (HRQOL) questionnaire across a treatment consisting of prism correction...
BACKGROUND
To track improvement in diplopia symptoms with strabismus-specific health-related quality of life (HRQOL) questionnaire across a treatment consisting of prism correction followed by vision therapy/orthoptics when prism treatment alone has not succeeded.
METHODS
Forty-eight participants with diplopia and a mean age of 62.45 were asked to complete an Adult Strabismus-20 (AS-20) questionnaire and a Diplopia Questionnaire (DQ) before and after prism correction. Inclusion criteria were diplopia reported on the DQ as "sometimes", "often" or "always" at reading or straight-ahead distance. The prism correction was classified as successful if the participant reported "never" or "rarely" on the DQ for reading and straight-ahead distance; and unsuccessful if the perceived diplopia worsened or remained the same. For all participants, mean initial AS-20 scores were compared with mean post-prism correction scores, taking into account AS-20 subscales (reading and general functions, and self-perception and interaction). Participants in the failed prism treatment subgroup subsequently underwent a programme of vision therapy wearing their prism correction, the results of which were again determined by participants' responses on the AS-20 questionnaire, completed before and after the vision therapy.
RESULTS
Five of the 48 participants dropped out of the study. Prism correction was classified as successful in 22 of 43 participants (51%), and unsuccessful in 21 (49%). Those participants for whom the prism correction was classified as a success showed a statistically significant improvement ( = 0.01) in both reading and general functions. In the failed treatment subgroup, no significant change in AS-20 score was recorded for any of the domains ( = 0.1). After treatment with vision therapy/orthoptics, however, 13 of the 20 participants in the unsuccessful prism correction subgroup (one of them dropped out the study) achieved binocular vision and statistically significant improvement in reading and general functions ( = 0.01).
CONCLUSIONS
Although effective prism correction of diplopia is correlated with enhanced HRQOL, prism correction alone is frequently not sufficient to achieve this objective. In these cases, vision therapy/orthoptics treatment as a coadjutant to prism correction is shown to improve HRQOL.
Topics: Humans; Diplopia; Quality of Life; Male; Female; Middle Aged; Aged; Surveys and Questionnaires; Eyeglasses; Treatment Outcome; Adult; Orthoptics; Strabismus; Aged, 80 and over
PubMed: 38737743
DOI: 10.7717/peerj.17315 -
Tremor and Other Hyperkinetic Movements... 2024Opsoclonus is a rare disorder characterized by conjugate multidirectional, horizontal, vertical, and torsional saccadic oscillations, without intersaccadic interval,...
BACKGROUND
Opsoclonus is a rare disorder characterized by conjugate multidirectional, horizontal, vertical, and torsional saccadic oscillations, without intersaccadic interval, resulting from dysfunction within complex neuronal pathways in the brainstem and cerebellum. While most cases of opsoclonus are associated with autoimmune or paraneoplastic disorders, infectious agents, trauma, or remain idiopathic, opsoclonus can also be caused by medications affecting neurotransmission. This review was prompted by a case of opsoclonus occurring in a patient with Multiple System Atrophy, where amantadine, an NMDA-receptor antagonist, appeared to induce opsoclonus.
METHODS
Case report of a single patient and systematized review of toxic/drug-induced opsoclonus, selecting articles based on predefined criteria and assessing the quality of included studies.
RESULTS
The review included 30 articles encompassing 158 cases of toxic/drug-induced opsoclonus. 74% of cases were attributed to bark scorpion poisoning, followed by 9% of cases associated with chlordecone intoxication. The remaining cases were due to various toxics/drugs, highlighting the involvement of various neurotransmitters, including acetylcholine, glutamate, GABA, dopamine, glycine, and sodium channels, in the development of opsoclonus.
CONCLUSION
Toxic/drug-induced opsoclonus is very rare. The diversity of toxics/drugs impacting different neurotransmitter systems makes it challenging to define a unifying mechanism, given the intricate neuronal pathways underlying eye movement physiology and opsoclonus pathophysiology.
Topics: Humans; Male; Amantadine; Multiple System Atrophy; Ocular Motility Disorders; Aged
PubMed: 38737300
DOI: 10.5334/tohm.832 -
BMJ Case Reports May 2024
Topics: Humans; Scrub Typhus; Male; Ocular Motility Disorders; Anti-Bacterial Agents
PubMed: 38729659
DOI: 10.1136/bcr-2024-260304