Does Spinocerebellar ataxia 27B mimic cerebellar multiple system atrophy?

BACKGROUND: Whether spinocerebellar ataxia 27B (SCA27B) may present as a cerebellar multiple system atrophy (MSA-C) mimic remains undetermined. OBJECTIVES: To assess the prevalence of FGF14 (GAA)≥250 expansions in patients with MSA-C, to compare SCA27B and MSA-C clinical presentation and natural history. METHODS: FGF14 expansion screening combined with longitudinal deep-phenotyping in a prospective cohort of 195 patients with sporadic late-onset cerebellar ataxia. RESULTS: After a mean disease duration of 6.4 years, 111 patients were not meeting criteria for MSA-C while 24 and 60 patients had a final diagnosis of possible and probable MSA-C, respectively. 16 patients carried an FGF14 (GAA)≥250 expansion in the group not meeting MSA-C criteria (14.4%), 3 patients in the possible MSA-C group (12.5%), but none among probable MSA-C cases. SCA27B patients were evolving more slowly than probable MSA-C patients. CONCLUSIONS: FGF14 (GAA)≥250 expansion may account for MSA look-alike cases and should be screened among slow progressors.

Natural History and Phenotypic Spectrum of GAA-FGF14 Sporadic Late-Onset Cerebellar Ataxia (SCA27B).

BACKGROUND: Heterozygous GAA expansions in the FGF14 gene have been related to autosomal dominant cerebellar ataxia (SCA27B-MIM:620174). Whether they represent a common cause of sporadic late-onset cerebellar ataxia (SLOCA) remains to be established. OBJECTIVES: To estimate the prevalence, characterize the phenotypic spectrum, identify discriminative features, and model longitudinal progression of SCA27B in a prospective cohort of SLOCA patients. METHODS: FGF14 expansions screening combined with longitudinal deep-phenotyping in a prospective cohort of 118 SLOCA patients (onset >40 years of age, no family history of cerebellar ataxia) without a definite diagnosis. RESULTS: Prevalence of SCA27B was 12.7% (15/118). Higher age of onset, higher Spinocerebellar Degeneration Functional Score, presence of vertigo, diplopia, nystagmus, orthostatic hypotension absence, and sensorimotor neuropathy were significantly associated with SCA27B. Ataxia progression was ≈0.4 points per year on the Scale for Assessment and Rating of Ataxia. CONCLUSIONS: FGF14 expansion is a major cause of SLOCA. Our natural history data will inform future FGF14 clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

A rise in cases of nitrous oxide abuse: neurological complications and biological findings.

BACKGROUND: The recent lockdown due to the COVID-19 pandemic has been linked to a higher incidence of psychiatric manifestations and substance abuse. The recreative use of nitrous oxide is more and more widespread and neurological complications are frequent. METHODS: We report clinical characteristics and biological findings of five consecutive patients presenting to our tertiary care center between April 2020 and February 2021 with various neurological symptoms occurring after recent nitrous oxide abuse. RESULTS: Our patients presented with subacute combined degeneration of the spinal cord (4/5 patients) or with acute inflammatory demyelinating polyneuropathy (1/5 patients). No patient had reduced vitamin B-12 titer, but all had elevated blood levels of homocysteine and methylmalonic acid. This reflects the functional deficit in vitamin B-12 that can be linked to nitrous oxide consumption. After vitamin B-12 supplementation, clinical signs regressed at least partially in all 5 patients. CONCLUSION: We report an elevated incidence of neurological complications of nitrous oxide abuse occurring during the recent COVID-19 lockdown. Nitrous oxide abuse should be tracked down in patients presenting with compatible neurological symptoms and elevated homocysteinemia. Vitamin B-12 should be supplemented as soon as the diagnosis is made.

Progression of Nigrostriatal Denervation in Cerebellar Multiple System Atrophy: A Prospective Study.

OBJECTIVES: Nigrostriatal dopaminergic denervation (NSDD) remains poorly characterized in cerebellar multiple system atrophy (MSA-C). We aimed to study NSDD progression in MSA-C and evaluate the capacity for [123I]-FP-CIT-SPECT and parkinsonism to differentiate MSA-C from idiopathic late-onset cerebellar ataxia (ILOCA). METHODS: We included 85 patients successively referred for sporadic late-onset cerebellar ataxia (SLOCA). Every 6 months, SARA, UPDRS-III, and SDFS scores were measured, and MSA-C diagnostic criteria were searched for. Striatal/occipital dopaminergic binding ratio was evaluated every year with [123I]-FP-CIT-scintigraphy. RESULTS: After a mean follow-up of 33.8 months, 33 patients had probable MSA-C, 8 possible MSA-C, and 44 ILOCA. SARA and UPDRS-III scores worsened faster in the probable MSA-C group (p < 0.01) compared with the ILOCA group. The baseline striatal/occipital ratio was lower (2.3 vs 2.97; p < 0.01) and more decreasing among patients with probable MSA-C (p < 0.01). Weighting dysautonomia and parkinsonism and/or NSDD as additional and principal criterion, respectively, in the possible MSA-C diagnostic criteria slightly improved their specificity (81.6% vs 76.9%) and sensitivity (77.8% vs 72.2%) to predict a final diagnosis of probable MSA-C. DISCUSSION: Rapid symptom worsening and NSDD existence and progression predict MSA-C among patients with SLOCA. Parkinsonism, NSDD, and dysautonomia should be considered equivalent for possible MSA-C diagnosis.

Numerical modelling of MHD waves in the solar chromosphere.

Acoustic waves are generated by the convective motions in the solar convection zone. When propagating upwards into the chromosphere they reach the height where the sound speed equals the Alfvén speed and they undergo mode conversion, refraction and reflection. We use numerical simulations to study these processes in realistic configurations where the wavelength of the waves is similar to the length scales of the magnetic field. Even though this regime is outside the validity of previous analytic studies or studies using ray-tracing theory, we show that some of their basic results remain valid: the critical quantity for mode conversion is the angle between the magnetic field and the k-vector: the attack angle. At angles smaller than 30 degrees much of the acoustic, fast mode from the photosphere is transmitted as an acoustic, slow mode propagating along the field lines. At larger angles, most of the energy is refracted/reflected and returns as a fast mode creating an interference pattern between the upward and downward propagating waves. In three-dimensions, this interference between waves at small angles creates patterns with large horizontal phase speeds, especially close to magnetic field concentrations. When damping from shock dissipation and radiation is taken into account, the waves in the low-mid chromosphere have mostly the character of upward propagating acoustic waves and it is only close to the reflecting layer we get similar amplitudes for the upward propagating and refracted/reflected waves. The oscillatory power is suppressed in magnetic field concentrations and enhanced in ring-formed patterns around them. The complex interference patterns caused by mode-conversion, refraction and reflection, even with simple incident waves and in simple magnetic field geometries, make direct inversion of observables exceedingly difficult. In a dynamic chromosphere it is doubtful if the determination of mean quantities is even meaningful.

Geometrical properties of avalanches in self-organized critical models of solar flares.

We investigate the geometrical properties of avalanches in self-organized critical models of solar flares. Traditionally, such models differ from the classical sandpile model in their formulation of stability criteria in terms of the curvature of the nodal field, and belong to a distinct universality class. With a view toward comparing these properties to those inferred from spatially and temporally resolved flare observations, we consider the properties of avalanche peak snapshots, time-integrated avalanches in two and three dimensions, and the two-dimensional projections of the latter. The nature of the relationship between the avalanching volume and its projected area is an issue of particular interest in the solar flare context. Using our simulation results we investigate this relationship, and demonstrate that proper accounting of the fractal nature of avalanches can bring into agreement hitherto discrepant results of observational analyses based on simple, nonfractal geometries for the flaring volume.

Continuum analysis of an avalanche model for solar flares.

We investigate the continuum limit of a class of self-organized critical lattice models for solar flares. Such models differ from the classical numerical sandpile model in their formulation of stability criteria in terms of the curvature of the nodal field, and are known to belong to a different universality class. A fourth-order nonlinear hyperdiffusion equation is reverse engineered from the discrete model's redistribution rule. A dynamical renormalization-group analysis of the equation yields scaling exponents that compare favorably with those measured in the discrete lattice model within the relevant spectral range dictated by the sizes of the domain and the lattice grid. We argue that the fourth-order nonlinear diffusion equation that models the behavior of the discrete model in the continuum limit is, in fact, compatible with magnetohydrodynamics (MHD) of the flaring phenomenon in the regime of strong magnetic field and the effective magnetic diffusivity characteristic of strong MHD turbulence.