MRI correlates of Parkinson's disease progression: A voxel based morphometry study

We investigated structural brain differences between a group of early-mild PD patients at different phases of the disease and healthy subjects using voxel-based morphometry (VBM). 20 mild PD patients compared to 15 healthy at baseline and after 2 years of follow-up. VBM is a fully automated technique, which allows the identification of regional differences in the gray matter enabling an objective analysis of the whole brain between groups of subjects. With respect to controls, PD patients exhibited decreased GM volumes in right putamen and right parietal cortex. After 2 years of disease, the same patients confirmed GM loss in the putamen and parietal cortex; a significant difference was also observed in the area of pedunculopontine nucleus (PPN) and in the mesencephalic locomotor region (MLR). PD is associated with brain morphological changes in cortical and subcortical structures. The first regions to be affected in PD seem to be the parietal cortex and the putamen. A third structure that undergoes atrophy is the part of the inferior-posterior midbrain, attributable to the PPN and MLR. Our findings provide new insight into the brain involvement in PD and could contribute to a better understanding of the sequence of events occurring in these patients

Can Disruption of Basal Ganglia-Thalamocortical Circuit in Wilson Disease Be Associated with Juvenile Myoclonic Epilepsy Phenotype?

In this paper, we describe the multimodal MRI findings in a patient with Wilson disease and a seizure disorder, characterized by an electroclinical picture resembling juvenile myoclonic epilepsy. The brain structural MRI showed a deposition of ferromagnetic materials in the basal ganglia, with marked hypointensities in T2-weighted images of globus pallidus internus bilaterally. A resting-state fMRI study revealed increased functional connectivity in the patient, compared to control subjects, in the following networks: (1) between the primary motor cortex and several cortical regions, including the secondary somatosensory cortex and (2) between the globus pallidus and the thalamo-frontal network. These findings suggest that globus pallidus alterations, due to metal accumulation, can lead to a reduction in the normal globus pallidus inhibitory tone on the thalamo-(motor)-cortical pathway. This, in turn, can result in hyperconnectivity in the motor cortex circuitry, leading to myoclonus and tonic-clonic seizures. We suppose that, in this patient, Wilson disease generated a ‘lesion model’ of myoclonic epilepsy

Frequency and outcome of olfactory impairment and sinonasal involvement in hospitalized patients with COVID-19

Background: Olfactory dysfunction has shown to accompany COVID-19. There are varying data regarding the exact frequency in the various study population. The outcome of the olfactory impairment is also not clearly defined. Objective: To find the frequency of olfactory impairment and its outcome in hospitalized patients with positive swab test for COVID-19. Methods: This is a prospective descriptive study of 100 hospitalized COVID-19 patients, randomly sampled, from February to March 2020. Demographics, comorbidities, and laboratory findings were analyzed according to the olfactory loss or sinonasal symptoms. The olfactory impairment and sinonasal symptoms were evaluated by 9 Likert scale questions asked from the patients. Results: Ninety-two patients completed the follow-up (means 20.1 (± 7.42) days). Twenty-two (23.91) patients complained of olfactory loss and in 6 (6.52) patients olfactory loss was the first symptom of the disease. The olfactory loss was reported to be completely resolved in all but one patient. Thirty-nine (42.39) patients had notable sinonasal symptoms while rhinorrhea was the first symptom in 3 (3.26). Fifteen patients (16.3) had a taste impairment. Patients with sinonasal symptoms had a lower age (p = 0.01). There was no significant relation between olfactory loss and sinonasal symptoms (p = 0.07). Conclusions: Sudden olfactory dysfunction and sinonasal symptoms have a considerable prevalence in patients with COVID-19. No significant association was noted between the sinonasal symptoms and the olfactory loss, which may suggest that other mechanisms beyond upper respiratory tract involvement are responsible for the olfactory loss. © 2020, Fondazione Società Italiana di Neurologia

Adult-onset KMT2B-related dystonia

KMT2B-related dystonia (DYT-KMT2B, also known as DYT28) is an autosomal dominant neurological disorder characterized by varying combinations of generalized dystonia, psychomotor developmental delay, mild-to-moderate intellectual disability and short stature. Disease onset occurs typically before 10 years of age. We report the clinical and genetic findings of a series of subjects affected by adult-onset dystonia, hearing loss or intellectual disability carrying rare heterozygous KMT2B variants. Twelve cases from five unrelated families carrying four rare KMT2B missense variants predicted to impact protein function are described. Seven affected subjects presented with adult-onset focal or segmental dystonia, three developed isolated progressive hearing loss, and one displayed intellectual disability and short stature. Genome-wide DNA methylation profiling allowed to discriminate these adult-onset dystonia cases from controls and early-onset DYT-KMT2B patients. These findings document the relevance of KMT2B variants as a potential genetic determinant of adult-onset dystonia and prompt to further characterize KMT2B carriers investigating non-dystonic features

Attosecond imaging of molecular electronic wavepackets

International audienceA strong laser field may tunnel ionize a molecule from several orbitals simultaneously, forming an attosecond electron–hole wavepacket. Both temporal and spatial information on this wavepacket can be obtained through the coherent soft X-ray emission resulting from the laser-driven recollision of the liberated electron with the core. By characterizing the emission from aligned N 2 molecules, we demonstrate the attosecond contributions of the two highest occupied molecular orbitals. We determine conditions where they are disentangled in the real and imaginary parts of the emission dipole moment. This allows us to carry out a tomographic reconstruction of both orbitals with angstrom spatial resolution. Their coherent superposition provides experimental images of the attosecond wavepacket created in the ionization process. Our results open the prospect of imaging ultrafast intramolecular dynamics combining attosecond and angstrom resolutions

A plea for equitable global access to COVID‐19 diagnostics, vaccination and therapy: The NeuroCOVID‐19 Task Force of the European Academy of Neurology

Coronavirus disease 2019 (COVID‐19), a multi‐organ disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), continues to challenge health and care systems around the globe. The pandemic has disrupted acute neurology services and routine patient care and has impacted the clinical course in patients with chronic neurological disease. COVID‐19 appears to have exposed inequalities of societies and healthcare systems and had a disproportionate impact on already vulnerable communities. The next challenge will be to set up initiatives to stop disparities in all aspects related to COVID‐19. From the medical perspective, there is a need to consider inequalities in prevention, treatment and long‐term consequences. Some of the issues of direct relevance to neurologists are summarised. With this appraisal, the European Academy of Neurology NeuroCOVID‐19 Task Force intends to raise awareness of the potential impact of COVID‐19 on inequalities in healthcare and calls for action to prevent disparity at individual, national and supranational levels

EAN consensus statement for management of patients with neurological diseases during the COVID‐19 pandemic

Background and purpose The recent SARS‐CoV‐2 pandemic has posed multiple challenges to the practice of clinical neurology including recognition of emerging neurological complications and management of coexistent neurological diseases. In a fast‐evolving pandemic, evidence‐based studies are lacking in many areas. This paper presents European Academy of Neurology (EAN) expert consensus statements to guide neurologists caring for patients with COVID‐19. Methods A refined Delphi methodology was applied. In round 1, statements were provided by EAN scientific panels (SPs). In round 2, these statements were circulated to SP members not involved in writing them, asking for agreement/disagreement. Items with agreement >70% were retained for round 3, in which SP co‐chairs rated importance on a five‐point Likert scale. Results were graded by importance and reported as consensus statements. Results In round one, 70 statements were provided by 23 SPs. In round two, 259/1061 SP member responses were received. Fifty‐nine statements obtained >70% agreement and were retained. In round three, responses were received from 55 co‐chairs of 29 SPs. Whilst general recommendations related to prevention of COVID‐19 transmission had high levels of agreement and importance, opinion was more varied concerning statements related to therapy. Conclusion This is the first structured consensus statement on good clinical practice in patients with neurological disease during the COVID‐19 pandemic that provides immediate guidance for neurologists. In this fast‐evolving pandemic, a rapid response using refined Delphi methodology is possible, but guidance may be subject to change as further evidence emerges

Prognostic indicators and outcomes of hospitalised COVID-19 patients with neurological disease: An individual patient data meta-analysis

BACKGROUND: Neurological COVID-19 disease has been reported widely, but published studies often lack information on neurological outcomes and prognostic risk factors. We aimed to describe the spectrum of neurological disease in hospitalised COVID-19 patients; characterise clinical outcomes; and investigate factors associated with a poor outcome. METHODS: We conducted an individual patient data (IPD) meta-analysis of hospitalised patients with neurological COVID-19 disease, using standard case definitions. We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute. We analysed features associated with poor outcome (moderate to severe disability or death, 3 to 6 on the modified Rankin Scale) using multivariable models. RESULTS: We included 83 studies (31 unpublished) providing IPD for 1979 patients with COVID-19 and acute new-onset neurological disease. Encephalopathy (978 [49%] patients) and cerebrovascular events (506 [26%]) were the most common diagnoses. Respiratory and systemic symptoms preceded neurological features in 93% of patients; one third developed neurological disease after hospital admission. A poor outcome was more common in patients with cerebrovascular events (76% [95% CI 67-82]), than encephalopathy (54% [42-65]). Intensive care use was high (38% [35-41]) overall, and also greater in the cerebrovascular patients. In the cerebrovascular, but not encephalopathic patients, risk factors for poor outcome included breathlessness on admission and elevated D-dimer. Overall, 30-day mortality was 30% [27-32]. The hazard of death was comparatively lower for patients in the WHO European region. INTERPRETATION: Neurological COVID-19 disease poses a considerable burden in terms of disease outcomes and use of hospital resources from prolonged intensive care and inpatient admission; preliminary data suggest these may differ according to WHO regions and country income levels. The different risk factors for encephalopathy and stroke suggest different disease mechanisms which may be amenable to intervention, especially in those who develop neurological symptoms after hospital admission