GBA1 Variants and Parkinson’s Disease: Paving the Way for Targeted Therapy

Glucosylceramidase beta 1 (GBA1) variants have attracted enormous attention as the most promising and important genetic candidates for precision medicine in Parkinson’s disease (PD). A substantial correlation between GBA1 genotypes and PD phenotypes could inform the prediction of disease progression and promote the development of a preventive intervention for individuals at a higher risk of a worse disease prognosis. Moreover, the GBA1-regulated pathway provides new perspectives on the pathogenesis of PD, such as dysregulated sphingolipid metabolism, impaired protein quality control, and disrupted endoplasmic reticulum-Golgi trafficking. These perspectives have led to the development of novel disease-modifying therapies for PD targeting the GBA1-regulated pathway by repositioning treatment strategies for Gaucher’s disease. This review summarizes the current hypotheses on a mechanistic link between GBA1 variants and PD and possible therapeutic options for modulating GBA1-regulated pathways in PD patients.

Validation Study of the Official Korean Version of the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale

Background@#and Purpose: The Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) is widely used for estimating the symptoms of Parkinson’s disease. Translation and validation of the MDS-UPDRS is necessary for non-English speaking countries and regions. The aim of this study was to validate the Korean version of the MDS-UPDRS. @*Methods@#Altogether, 362 patients in 19 centers were recruited for this study. We translated the MDS-UPDRS to Korean using the translation-back translation method and cognitive pretesting. We performed both confirmatory and exploratory factor analyses to validate the scale.We calculated the comparative fit index (CFI) for confirmatory factor analysis, and used unweighted least squares for exploratory factor analysis. @*Results@#The CFI was higher than 0.90 for all parts of the scale. Exploratory factor analysis also showed that the Korean MDS-UPDRS has the same number of factors in each part as the English version. @*Conclusions@#The Korean MDS-UPDRS has the same overall structure as the English MDSUPDRS. Our translated scale can be designated as the official Korean MDS-UPDRS.

Atypical parkinsonism with marked asymmetry due to a superimposed developmental venous anomaly

@#Intracranial developmental venous anomalies (DVAs) are the most common cerebral vascular malformation and are usually asymptomatic. Movement disorders are rarely associated with DVAs within basal ganglia regions. We report a case of markedly asymmetric parkinsonism due to unilateral DVA in the basal ganglia, which occurred together with symmetrical nigrostriatal dopaminergic deficits. A 57-year-old woman presented with resting tremor in the right hand lasting for 6 months. She also experienced problems with gait and started falling while walking one month ago. The neurological examination found a resting tremor in the right hand and moderate rigidity and bradykinesia in the right extremities. She reported light headedness on standing up. The patient displayed minimal response to treatment with 300 mg levodopa. The FP-CIT PET scan revealed symmetrical decrease of radiotracer uptake in bilateral basal ganglia. Brain MRI and cerebral angiography identified a large DVA draining the basal ganglia, thalamus, and surrounding deep white matter in the left side. Conclusion: A DVA may contribute to the prominent asymmetrical manifestation in our patient, in combination with symmetrical dopaminergic loss from neurodegenerative Parkinsonian syndrome. A marked asymmetry in patients with signs of atypical Parkinsonism can be a clue for further imaging investigation to exclude superimposed structural lesions such as DVAs.

Bedside Evaluation of Dizzy Patients

In recent decades there has been marked progress in the imaging and laboratory evaluation of dizzy patients. However, detailed history taking and comprehensive bedside neurotological evaluation remain crucial for a diagnosis of dizziness. Bedside neurotological evaluation should include examinations for ocular alignment, spontaneous and gaze-evoked nystagmus, the vestibulo-ocular reflex, saccades, smooth pursuit, and balance. In patients with acute spontaneous vertigo, negative head impulse test, direction-changing nystagmus, and skew deviation mostly indicate central vestibular disorders. In contrast, patients with unilateral peripheral deafferentation invariably have a positive head impulse test and mixed horizontal-torsional nystagmus beating away from the lesion side. Since suppression by visual fixation is the rule in peripheral nystagmus and is frequent even in central nystagmus, removal of visual fixation using Frenzel glasses is required for the proper evaluation of central as well as peripheral nystagmus. Head-shaking, cranial vibration, hyperventilation, pressure to the external auditory canal, and loud sounds may disclose underlying vestibular dysfunction by inducing nystagmus or modulating the spontaneous nystagmus. In patients with positional vertigo, the diagnosis can be made by determining patterns of the nystagmus induced during various positional maneuvers that include straight head hanging, the Dix-Hallpike maneuver, supine head roll, and head turning and bending while sitting. Abnormal smooth pursuit and saccades, and severe imbalance also indicate central pathologies. Physicians should be familiar with bedside neurotological examinations and be aware of the clinical implications of the findings when evaluating dizzy patients.

Isolated Inferior Rectus Palsy from Midbrain Infarction

No abstract available.

Ipsilateral Axial Lateropulsion as an Initial Symptom of Lateral Medullary Infarction: a Case Report

The dorsolateral medullary syndrome (Wallenberg's syndrome) is produced by infarction of a wedge of lateral medulla posterior to the inferior olivary nucleus, and is usually caused by vertebral artery occlusion. Ipsilateral axial lateropulsion as an initial symptom of vertebral artery occlusion is rare, and the responsible anatomical structure is still uncertain. Here we describe a patient presenting with ipsilateral axial lateropulsion as an initial symptom of vertebral artery occlusion.