Trigeminal Neuralgia Associated With a Solitary Pontine Lesion: A Case Report.

Trigeminal neuralgia associated with brainstem lesions is currently considered as a rare condition and only few patients have been reported so far in literature. Tohyama and colleagues recently proposed the nosological entity of trigeminal neuralgia associated with solitary pontine lesion, trying to categorize it as a new clinical syndrome on its own. Based on this description, trigeminal neuralgia associated with solitary pontine lesion patients have an identical clinical presentation compared to other patients with trigeminal neuralgia but have a solitary pontine lesion. The nature of the pontine lesion has been attributed to several etiologies, including ischemia, demyelination or previous pontine viral neuritis. In those patients with a putative demyelinating lesion, a definite diagnosis of multiple sclerosis cannot be made due to the lack of dissemination in space. Very little is known in relation to the cerebrospinal fluid characteristics of this population of patients. We present a case of a 42-year-old man suffering of trigeminal neuralgia associated with solitary pontine lesion with a possible demyelinating etiology. The patient herein described had an atypical trigeminal neuralgia associated with a single pontine lesion. The MRI characteristics of the lesion, along with the presence of oligoclonal bands in the cerebrospinal fluid, suggested a demyelinating etiology. Trigeminal neuralgia associated with a solitary pontine lesion may be categorized as a possible manifestation of solitary sclerosis. Future research need to reveal which features can predict the risk of conversion to clinically defined multiple sclerosis and which treatments modify this risk.

Magnetic resonance metrics to evaluate the effect of therapy in amyotrophic lateral sclerosis: the experience with edaravone.

BACKGROUND: Edaravone was approved as a new treatment for amyotrophic lateral sclerosis (ALS), although there are different opinions on its effectiveness. Magnetic resonance (MRI) measures appear promising as diagnostic and prognostic indicators of disease. However, published studies on MRI using to monitor treatment efficacy in ALS are lacking. PURPOSE: The objective of this study was to investigate changes in brain MRI measures in patients treated with edaravone. METHODS: Thirteen ALS patients assuming edaravone (ALS-EDA) underwent MRI at baseline (T0) and after 6 months (T6) to measure cortical thickness (CT) and fractional anisotropy (FA) of white matter (WM) tracts. MRI data of ALS-EDA were compared at T0 with those of 12 control subjects (CS), and at T6 with those of 11 ALS patients assuming only riluzole (ALS-RIL), extracted from our ALS cohort using a propensity-score-matching. A longitudinal MRI analysis was performed in ALS-EDA between T6 and T0. RESULTS: At T0, ALS-EDA showed a cortical widespread thinning in both hemispheres, particularly in the bilateral precentral gyrus, and a reduction of FA in bilateral corticospinal tracts, in comparison to CS. Thinning in bilateral precentral cortex and significant widespread reduction of FA in several WM tracts were observed in ALS-EDA at T6 compared to T0. At T6, no significant differences in MRI measures of ALS-EDA versus ALS-RIL were found. CONCLUSIONS: Patients treated with edaravone showed progression of damage in the motor cortex and several WM tracts, at a six-month follow-up. Moreover, this study showed no evidence of a difference between edaravone and riluzole.

Dysregulation of MicroRNAs and Target Genes Networks in Peripheral Blood of Patients With Sporadic Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease. While genetics and other factors contribute to ALS pathogenesis, critical knowledge is still missing and validated biomarkers for monitoring the disease activity have not yet been identified. To address those aspects we carried out this study with the primary aim of identifying possible miRNAs/mRNAs dysregulation associated with the sporadic form of the disease (sALS). Additionally, we explored miRNAs as modulating factors of the observed clinical features. Study included 56 sALS and 20 healthy controls (HCs). We analyzed the peripheral blood samples of sALS patients and HCs with a high-throughput next-generation sequencing followed by an integrated bioinformatics/biostatistics analysis. Results showed that 38 miRNAs (let-7a-5p, let-7d-5p, let-7f-5p, let-7g-5p, let-7i-5p, miR-103a-3p, miR-106b-3p, miR-128-3p, miR-130a-3p, miR-130b-3p, miR-144-5p, miR-148a-3p, miR-148b-3p, miR-15a-5p, miR-15b-5p, miR-151a-5p, miR-151b, miR-16-5p, miR-182-5p, miR-183-5p, miR-186-5p, miR-22-3p, miR-221-3p, miR-223-3p, miR-23a-3p, miR-26a-5p, miR-26b-5p, miR-27b-3p, miR-28-3p, miR-30b-5p, miR-30c-5p, miR-342-3p, miR-425-5p, miR-451a, miR-532-5p, miR-550a-3p, miR-584-5p, miR-93-5p) were significantly downregulated in sALS. We also found that different miRNAs profiles characterized the bulbar/spinal onset and the progression rate. This observation supports the hypothesis that miRNAs may impact the phenotypic expression of the disease. Genes known to be associated with ALS (e.g., PARK7, C9orf72, ALS2, MATR3, SPG11, ATXN2) were confirmed to be dysregulated in our study. We also identified other potential candidate genes like LGALS3 (implicated in neuroinflammation) and PRKCD (activated in mitochondrial-induced apoptosis). Some of the downregulated genes are involved in molecular bindings to ions (i.e., metals, zinc, magnesium) and in ions-related functions. The genes that we found upregulated were involved in the immune response, oxidation-reduction, and apoptosis. These findings may have important implication for the monitoring, e.g., of sALS progression and therefore represent a significant advance in the elucidation of the disease's underlying molecular mechanisms. The extensive multidisciplinary approach we applied in this study was critically important for its success, especially in complex disorders such as sALS, wherein access to genetic background is a major limitation.

Diagnostic and prognostic power of CSF Tau in amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that still lacks reliable diagnostic biomarkers. This study aims to evaluate the diagnostic and prognostic potential of CSF total Tau (t-Tau), phospho-Tau (p-Tau) and p-Tau/t-Tau ratio in ALS patients using CSF neurofilament light (NFL) as the reference biomarker. METHODS: Eighty-five incident ALS, 30 ALS-mimicking (AM) diseases and 51 other non-neurodegenerative diseases (ONND) were included in the study. RESULTS: ALS patients had higher levels of CSF t-Tau and lower p-Tau/t-Tau ratio than AM (p = 0.005 and p = 0.006) and ONND (p < 0.001). CSF t-Tau levels discriminated ALS from AM with a sensitivity of 69% and specificity of 60%, and from ONND with a sensitivity of 88% and specificity of 51%. These values were lower than the accuracy of CSF NFL in ALS (sensitivity 86% and specificity 87% in distinguishing ALS from AM and sensitivity 83% and specificity 75% from ONND); CSF t-Tau correlated with progression rate and SNIP. CSF p-Tau did not show relation with any ALS clinical features. CSF NFL significantly correlated with all considered clinical parameters. High levels of CSF t-Tau and NFL were related to poor survival. CONCLUSION: CSF t-Tau showed no reliable diagnostic significance but the relation between the high levels of CSF t-Tau and short survival suggests the potential prognostic role of this biomarker in ALS. However, CSF NFL was confirmed to be the most reliable and efficient tool for diagnosis and prediction of clinical progression and survival in ALS patients.

Adherence to riluzole in patients with amyotrophic lateral sclerosis: an observational study.

OBJECTIVE: Riluzole is the first drug approved to treat amyotrophic lateral sclerosis (ALS). Recently, an oral suspension (OS) of riluzole was made available. Thus, the aim of our study was to evaluate the adherence to 2 formulations of riluzole in patients with ALS. PATIENTS AND METHODS: We enrolled 45 consecutive patients with ALS. At disease diagnosis, riluzole was prescribed in 2 different formulations depending on the severity of dysphagia (27/45 patients received tablets and 18/45 patients received OS). Side effects (SEs) and treatment adherence were investigated using a clinical questionnaire including the ©Morisky 8-item Medication Adherence Questionnaire. RESULTS: Gastroenteric complaints were the most frequent SEs (58% in the tablet group and 48% in the OS group), followed by those at the nervous system (29% and 40%, respectively). No serious SEs related to treatment were reported. The rate of adherence to riluzole was independent of the formulation of the drug and consistent with other medications assumed for comorbidities (p=0.004). In the tablet group, low adherence was caused by SEs in 55.6% and by dysphagia in 44.4% of patients. In the OS group, SEs caused low adherence in 75% of patients. Independently of the drug formulation, patients with high or medium adherence to riluzole had a higher progression rate (p=0.002 and p=0.009, respectively) and a shorter time to generalization (TTG; p=0.01), compared to those with low adherence. CONCLUSION: Gastroenteric symptoms were the most frequent SE related to tablet as well as OS. The rate of adherence was independent of the formulation of riluzole and the number of medications assumed for comorbidities, and it was consistent with the severity of the disease. The low adherence was caused by dysphagia and SEs in the tablet group, whereas it was caused prevalently by SEs in the OS group.

Corrigendum: Dysregulation of MicroRNAs and Target Genes Networks in Peripheral Blood of Patients With Sporadic Amyotrophic Lateral Sclerosis.

[This corrects the article DOI: 10.3389/fnmol.2018.00288.].

Cortical thinning and clinical heterogeneity in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) has heterogeneous clinical features that could be translated into specific patterns of brain atrophy. In the current study we have evaluated the relationship between different clinical expressions of classical ALS and measurements of brain cortical thickness. Cortical thickness analysis was conducted from 3D-MRI using FreeSurfer software in 29 ALS patients and 20 healthy controls. We explored three clinical traits of the disease, subdividing the patients into two groups for each of them: the bulbar or spinal onset, the higher or lower upper motor neuron burden, the faster or slower disease progression. We used both a whole brain vertex-wise analysis and a ROI analysis on primary motor areas. ALS patients showed cortical thinning in bilateral precentral gyrus, bilateral middle frontal gyrus, right superior temporal gyrus and right occipital cortex. ALS patients with higher upper motor neuron burden showed a significant cortical thinning in the right precentral gyrus and in other frontal extra-motor areas, compared to healthy controls. ALS patients with spinal onset showed a significant cortical thinning in the right precentral gyrus and paracentral lobule, compared to healthy controls. ALS patients with faster progressive disease showed a significant cortical thinning in widespread bilateral frontal and temporal areas, including the bilateral precentral gyrus, compared to healthy controls. Focusing on the primary motor areas, the ROI analysis revealed that the mean cortical thickness values were significantly reduced in ALS patients with higher upper motor neuron burden, spinal onset and faster disease progression related to healthy controls. In conclusion, the thickness of primary motor cortex could be a useful surrogate marker of upper motor neuron involvement in ALS; also our results suggest that cortical thinning in motor and non motor areas seem to reflect the clinical heterogeneity of the disease.

Amyotrophic lateral sclerosis: a new missense mutation in the SOD1 gene.

Copper-zinc superoxide dismutase-1 (SOD1) is the second most common mutated gene in amyotrophic lateral sclerosis (ALS). To date more than 150 missense mutations of SOD1 have been reported. The objective of this study was to describe a novel SOD1 mutation and its phenotypic expression. We describe a 74-year-old Caucasian man who began to complain of progressive weakness and atrophy of the right hand and over 10 months developed a severe tetraparesis, with atrophies of upper and lower limbs and neck muscles, dysphagia, and dyspnea that led to percutaneous endoscopic gastrostomy and tracheotomy. A diagnosis of ALS was made. Genetic analysis identified a heterozygous mutation in exon 4 of SOD1 that results in the amino acid substitution from arginine to cysteine at position 115 (p.R115C). We identified a novel pathogenic SOD1 mutation in a patient with a very rapid disease progression and aggressive phenotype providing additional information on the wide range of SOD1 mutations in apparently sporadic ALS and confirming the possibility of a strong genotype-phenotype correlation for distinct SOD1 mutations.