Parkinson's disease and vitamins: a focus on vitamin B12.

Parkinson's disease (PD) has been linked to a vast array of vitamins among which vitamin B12 (Vit B12) is the most relevant and often investigated specially in the context of intrajejunal levodopa infusion therapy. Vit B12 deficiency, itself, has been reported to cause acute parkinsonism. Nevertheless, concrete mechanisms through which B12 deficiency interacts with PD in terms of pathophysiology, clinical manifestation and progression remains unclear. Recent studies have suggested that Vit B12 deficiency along with the induced hyperhomocysteinemia are correlated with specific PD phenotypes characterized with early postural instability and falls and more rapid motor progression, cognitive impairment, visual hallucinations and autonomic dysfunction. Specific clinical features such as polyneuropathy have also been linked to Vit B12 deficiency specifically in context of intrajejunal levodopa therapy. In this review, we explore the link between Vit B12 and PD in terms of physiopathology regarding dysfunctional neural pathways, neuropathological processes as well as reviewing the major clinical traits of Vit B12 deficiency in PD and Levodopa-mediated neuropathy. Finally, we provide an overview of the therapeutic effect of Vit B12 supplementation in PD and posit a practical guideline for Vit B12 testing and supplementation.

Eye movement study in essential tremor patients and its clinical correlates.

Essential tremor (ET) encompasses a wide spectrum of motor and non-motor features. Eye movement abnormalities were first reported two decades ago as an atypical finding in ET. Today, a growing number of publications about eye movement abnormalities in neurodegenerative diseases have helped understand their pathophysiology and the basis of their phenotypic variability. Thus, addressing such aspect in ET may disentangle, based on the oculomotor network abnormalities, the dysfunctional brain pathways in ET. In this study, we aimed to describe neurophysiological eye movement abnormalities in ET and their clinical correlates in terms of cognition and other associated clinical signs. We conducted a cross-sectional study in a tertiary neurology referral center including consecutive ET patients and cognitively normal healthy controls (HC) matched for age and sex. The study protocol included the assessment of voluntary horizontal saccades, smooth pursuit, anti-saccades and saccadic intrusions. We assessed the associated motor signs, cognitive functions and the presence of rapid eye movement disorder (RBD). Sixty-two ET patients and 66 HC were enrolled in the study. Eye movement examination showed significant abnormalities in comparison with HC (46.7% vs 20%, p = 0.002). Prolonged saccadic latency (38.7%, p = 0.033) and altered smooth pursuit (38.7%, p = 0.033) were the most common abnormalities in ET patients. Anti-saccadic errors (16% vs 0% in HC, p = 0.034) correlated with the presence of rigidity (p = 0.046), bradykinesia (p = 0.001), cognitive dysfunction (p = 0.006), executive dysfunction (p = 0.0002), apraxia (p = 0.0001), altered verbal fluency (p = 0.013) and altered backward digit span (p = 0.045) along with the presence of RBD (p = 0.035). Square-wave jerks (11.5% vs 0% in HC, p = 0.0024) correlated with rest tremor. A distinctive phenotype of ET could emerge out of this study characterized by anti-saccadic errors and a sub-cortical cognitive profile, consecutive to the disruption of the cerebello-thalamo-cortical loop. Patients with anti-saccadic errors could be cognitively vulnerable and in need of a close monitoring of their cognitive efficiency during the disease's progression. They may as well convert to Parkinson disease if they present with parkinsonism, RBD and square-wave jerks and require, consequently, a close observation of their motor progression.

Non-motor features of essential tremor with midline distribution.

BACKGROUND: Midline essential tremor (Mid-ET) is a distinctive group of essential tremor (ET) in which tremor affects the neck, jaw, tongue, and/or voice. For long, it has been considered as an ultimate stage of the disease and a marker of its severity. However, recent studies pointed its complexity in terms of non-motor presentation. Thus, we aimed to investigate the non-motor signs (NMS) in Mid-ET. DESIGN: We conducted a cross-sectional study in a tertiary neurology referral center including ET patients classified into two groups based on the presence or not of midline tremor (Mid-ET vs. No-Mid-ET). We assessed NMS using the non-motor severity scale (NMSS), a large battery of cognitive tests, clinical and electrophysiological study of the autonomic nervous system along with the evaluation of sleep disturbances. RESULTS: A total of 163 patients were included: Mid-ET (n = 79) and No-Mid-ET (n = 84) matched in gender and age of onset. Mid-ET patients had higher proportion of late-onset ET (> 60 years old, p = 0.002) and more extrapyramidal signs (p = 0.005). For NMS, Mid-ET was marked with cognitive dysfunction (p = 0.008). The hallmarks of the neuropsychiatric profile of Mid-ET were executive dysfunction (p = 0.004), attention problems (p < 0.000), episodic memory impairment (p = 0.003), and greater depression (p = 0.010). The presence of RBD was a trait of Mid-ET (p = 0.039). In both Mid-ET and No-Mid-ET phenotypes, clinical and neurophysiological dysautonomia correlated with cognitive dysfunction. CONCLUSION: Mid-ET patients had greater cognitive dysfunction, depression, RBD, higher proportion of late-onset ET, and more extrapyramidal signs. Taken all together, these findings could provide a redesigned insight into the underlying physiopathology of Mid-ET indicative of a greater cerebellar dysfunction.

Eye Movement Abnormalities in Amyotrophic Lateral Sclerosis in a Tunisian Cohort.

Few studies have reported abnormal ocular movements in cases of amyotrophic lateral sclerosis (ALS) and their link with other disease features. Our study aimed to describe and analyse eye movement abnormalities in ALS patients. Specifically, we set out to investigate the correlation between non-motor signs and oculomotor impairment in order to understand the pathogenesis of the disease. All ALS patients seen from 2018 to 2020 in the department of Neurology of Razi hospital underwent the recording of saccadic eye movements. Results were compared with healthy controls. Sixty-two patients were included. Altered saccadic eye movements (72.6%) correlated with tongue atrophy and bladder dysfunction. The most common finding was altered smooth pursuit (56.5%), which showed correlation with bladder dysfunction and altered frontal assessment battery (FAB) scores. Prolonged latencies of horizontal saccades (34%) correlated with sensory and extrapyramidal signs. Our study is the first to examine the characteristics of eye movements in a large African cohort of ALS patients and to show correlations with extra-motor clinical signs. Our findings showed extra-motor cortex dysfunction in ALS with greater frequency of eye movement abnormalities in comparison with previous studies. Altered horizontal pursuit, the core abnormality, confirmed the extension of the neurodegenerative process to the frontal and prefrontal cortices. Prolonged horizontal saccade latencies reflect mainly the involvement of the parietal eye field. Anti-saccadic abnormalities were the least common finding and showed, paradoxically, no link with executive dysfunction.

Brain atrophy patterns in multiple sclerosis patients treated with natalizumab and its clinical correlates.

BACKGROUND: Multiple sclerosis (MS) is defined as a demyelinating disorder of the central nervous system, witnessing over the past years a remarkable progress in the therapeutic approaches of the inflammatory process. Yet, the ongoing neurodegenerative process is still ambiguous, under-assessed, and probably under-treated. Atrophy and cognitive dysfunction represent the radiological and clinical correlates of such process. In this study, we evaluated the effect of one specific MS treatment, which is natalizumab (NTZ), on brain atrophy evolution in different anatomical regions and its correlation with the cognitive profile and the physical disability. METHODS: We recruited 20 patients diagnosed with relapsing-remitting MS (RR-MS) and treated with NTZ. We tracked brain atrophy in different anatomical structures using MRI scans processed with an automated image segmentation technique. We also assessed the progression of physical disability and the cognitive function and its link with the progression of atrophy. RESULTS: During the first 2 years of treatment, a significant volume loss was noted within the corpus callosum and the cerebellum gray matter (GM). The annual atrophy rate of the cortical GM, the cerebellum GM, the thalamus, the amygdala, the globus pallidus, and the hippocampus correlated with greater memory impairment. As for the third and fourth years of treatment, a significant atrophy revolved around the gray matter, mainly the cortical one. We also noted an increase of the thalamus volume. CONCLUSION: Atrophy in RR-MS patients treated with NTZ is regional and targeting highly cognitive regions mainly of the subcortical gray matter and the cerebellum. The cerebellum atrophy was a marker of physical disability progression. NTZ did not accelerate the atrophy process in MS and may play a neuroprotective role by increasing the thalamus volume.