Neurological disorders in COVID-19: a case of Acute Disseminated Encephalomyelitis in an adult patient

Different neurological complications associated with the severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection have been widely documented. Acute disseminated encephalomyelitis (ADEM) is a rare immune-mediated demyelinating disorder, described within the spectrum of neurological manifestations of COVID-19. Herein, we describe a case of adult-ADEM presenting with diplopia and slowly progressive ataxia developed one month after SARS-CoV-2 infection. Brain magnetic resonance imaging (MRI) revealed acute multifocal demyelinating lesions throughout the brain. Other possible etiologies have been ruled out. After treatment with high-dose steroids, we observed a progressive clinical and radiological improvement. A 4-months follow-up showed complete clinical recovery. Although extremely rare, ADEM could be associated to SARS-CoV-2 infection and should be considered in the differential diagnosis. Early recognition of this COVID-19 neurological complication, even in the absence of pulmonary involvement, is important to start a prompt immune-modulatory treatment and, consequently, ensure a good outcome

Pre- and Post-surgical Poor Seizure Control as Hallmark of Malignant Progression in Patients With Glioma?

BackgroundRegarding brain tumor-related epilepsy (BTRE), there is an increasing number of evidence about a relationship between epileptogenesis and oncogenesis. A recent study suggests a role of post-surgery seizure outcome on the survival of patients with low-grade glioma (LGG), underlying the need for a targeted and aggressive epilepsy treatment. ObjectiveThis study aims at investigating the possible correlation between pre- and post-surgical seizure control and tumor progression in patients who underwent surgery for LGG. MethodsWe performed a retrospective analysis of patients affected by LGGs and BTRE, in a single high-volume neurosurgical center. Seizure control was assessed before surgery and at 3 years of follow-up. Patients with histological progression in high-grade glioma (HGG) have been evaluated. Clinical features, pre-surgical electroencephalograms (EEGs), and electrocorticography (ECoG) have been analyzed. ResultsAmong 154 subjects, we collected 32 patients who presented a tumor progression in HGG during the follow-up period. The majority had poor seizure control both pre- and post-surgery, never being in Engel class Ia throughout the whole history of their disease. Almost all patients with poor seizure control had pathological ECoG recording. Clinical features of seizures did not correlate with seizure outcome. On the univariate analysis, the age, the post-operative Engel class, and the extent of resection (EOR) were the prognostic factors significantly associated with oncological outcome; nevertheless, on multivariate analysis, Engel class significance was not confirmed, and the only predicting factor were age and EOR. ConclusionsAlthough not confirmed on multivariate analysis, post-surgical seizure control could be a relevant factor to consider during follow-up of BRTE, in particular, when gross total resection is not achieved. Pathological findings on the ECoG may suggest a "hidden" propensity to malignant progression, strictly related to the persistent neuronal hyper-excitability. Further studies with longer follow-up period are needed to confirm our observations

Post-Stroke Status Epilepticus: Time of Occurrence May Be the Difference?

(1) Background: Stroke is one of the most frequent causes of status epilepticus (SE) in adults. Patients with stroke and SE have poorer prognosis than those with stroke alone. We described characteristics and prognosis of early- and late-onset post-stroke SE (PSSE). (2) Methods: We retrospectively analyzed consecutive stroke patients who experienced a first SE between August 2012 and April 2021, comparing clinical characteristics, stroke, and SE features between early- versus late-onset SE in relation to patients' outcome. (3) Results: Forty stroke patients experienced PSSE. Fourteen developed an early-onset SE (35%) and twenty-six a late-onset SE (65%). Early-onset SE patients had a slightly higher NIHSS score at admission (6.9 vs. 6.0; p = 0.05). Early-onset SE was more severe than late-onset, according to STESS (Status Epilepticus Severity Score) (3.5 vs. 2.8; p = 0.05) and EMSE (Epidemiology-based Mortality score in Status Epilepticus) score (97.0 vs. 69.5; p = 0.04); furthermore, it had a significant impact on disability at 3-month and 1-year follow-up (p = 0.03 and p = 0.02). SE recurrence and seizures relapse were observed mainly in cases of late-onset SE. (4) Conclusions: Early-onset SE seems to be associated with higher disability in short- and long-term follow-up as possible expression of severe acute brain damage

Recurrent Status Epilepticus and SARS-CoV-2 infection: the "perfect storm"

Respiratory involvement is the most common clinical manifestation of COVID-19, but neurological symptoms and complications are increasingly being recognized. Seizures and status epilepticus (SE) have been described as possible consequences of hypoxia and metabolic derangements during SARS-CoV-2 infection, direct viral invasion of the central nervous system, or as para or post-infectious complications. Single episodes of SE have been described, occurring during the acute phase of COVID-19 or once the patients have been recovered. Herein, we present the case of a patient with a positive serology test for SARS-CoV-2 (IgG+, IgM-) and recurrent SE occurring within 36 days. Diagnostic work-up ruled out other known causes of SE. A post-COVID-19 infectious inflammatory/immune response is hypothesized as the possible trigger of SE

Whole-exome sequencing in patients with protein aggregate myopathies reveals causative mutations associated with novel atypical phenotypes

BACKGROUND: Myofibrillar myopathies (MFM) are a subgroup of protein aggregate myopathies (PAM) characterized by a common histological picture of myofibrillar dissolution, Z-disk disintegration, and accumulation of degradation products into inclusions. Mutations in genes encoding components of the Z-disk or Z-disk-associated proteins occur in some patients whereas in most of the cases, the causative gene defect is still unknown. We aimed to search for pathogenic mutations in genes not previously associated with MFM phenotype.METHODS: We performed whole-exome sequencing in four patients from three unrelated families who were diagnosed with PAM without aberrations in causative genes for MFM.RESULTS: In the first patient and her affected daughter, we identified a heterozygous p.(Arg89Cys) missense mutation in LMNA gene which has not been linked with PAM pathology before. In the second patient, a heterozygous p.(Asn4807Phe) mutation in RYR1 not previously described in PAM represents a novel, candidate gene with a possible causative role in the disease. Finally, in the third patient and his symptomatic daughter, we found a previously reported heterozygous p.(Cys30071Arg) mutation in TTN gene that was clinically associated with cardiac involvement.CONCLUSIONS: Our study identifies a new genetic background in PAM pathology and expands the clinical phenotype of known pathogenic mutations

Prevalence of Spinal Muscular Atrophy in the Era of Disease-Modifying Therapies: An Italian Nationwide Survey

Objective: Spinal muscular atrophy (SMA) is a neurodegenerative disorder caused by mutations in the SMN1 gene. The aim of this study was to assess the prevalence of SMA and treatment prescription in Italy. Methods: An online survey was distributed to 36 centers identified by the Italian government as referral centers for SMA. Data on the number of patients with SMA subdivided according to age, type, SMN2 copy number, and treatment were collected. Results: One thousand two hundred fifty-five patients with SMA are currently followed in the Italian centers with an estimated prevalence of 2.12/100,000. Of the 1,255, 284 were type I, 470 type II, 467 type III, and 15 type IV with estimated prevalence of 0.48, 0.79, 0.79 and 0.02/100,000, respectively. Three patients with SMA 0 and 16 presymptomatic patients were also included. Approximately 85% were receiving one of the available treatments. The percentage of treated patients decreased with decreasing severity (SMA I: 95.77%, SMA II: 85.11%, SMA III: 79.01%). Discussion: The results provide for the first time an estimate of the prevalence of SMA at the national level and the current distribution of patients treated with the available therapeutical options. These data provide a baseline to assess future changes in relation to the evolving therapeutical scenario

Evaluating the SERCA2 and VEGF mRNAs as Potential Molecular Biomarkers of the Onset and Progression in Huntington's Disease

Abnormalities of intracellular Ca2+ homeostasis and signalling as well as the down-regulation of neurotrophic factors in several areas of the central nervous system and in peripheral tissues are hallmarks of Huntington\u2019s disease (HD). As there is no therapy for this hereditary, neurodegenerative fatal disease, further effort should be made to slow the progression of neurodegeneration in patients through the definition of early therapeutic interventions. For this purpose, molecular biomarker(s) for monitoring disease onset and/or progression and response to treatment need to be identified. In the attempt to contribute to the research of peripheral candidate biomarkers in HD, we adopted a multiplex real-time PCR approach to analyse the mRNA level of targeted genes involved in the control of cellular calcium homeostasis and in neuroprotection. For this purpose we recruited a total of 110 subjects possessing the HD mutation at different clinical stages of the disease and 54 sex- and agematched controls. This study provides evidence of reduced transcript levels of sarco-endoplasmic reticulum-associated ATP2A2 calcium pump (SERCA2) and vascular endothelial growth factor (VEGF) in peripheral blood mononuclear cells (PBMCs) of manifest and premanifest HD subjects. Our results provide a potentially new candidate molecular biomarker for monitoring the progression of this disease and contribute to understanding some early events that might have a role in triggering cellular dysfunctions in HD

Formal semantics in the neurology clinic: Atypical understanding of aspectual coercion in ALS patients

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the motor system with subtle adverse effects on cognition. It is still unclear whether ALS also affects language and semantics, and if so, what aspects and processes exactly. We investigated how ALS patients understand verb phrases modified by temporal preposition phrases, e.g., “To watch TV for half an hour.” Interpretation here requires operations such as aspectual coercion that add or delete elements from event structures, depending on temporal modifiers, and constraints on coercion, which make combinations with certain modifiers not viable. Using a theoretically-motivated experimental design, we observed that acceptance rates for aspectual coercion were abnormally high in ALS patients. The effect was largest for the more complex cases of coercion: not those that involve enrichment of event structures (“To switch on the TV in half an hour,” where a number of failed attempts must be included in the interpretation) but those that, if applied, would result in deletion of event structure elements (“To repair the TV for half an hour”). Our experimental results are consistent with a deficit of constraints on coercion, and not with impaired semantic processes or representations, in line with recent studies suggesting that verb semantics is largely spared in ALS

Formal semantics in the neurology clinic: Atypical understanding of aspectual coercion in ALS patients

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the motor system with subtle adverse effects on cognition. It is still unclear whether ALS also affects language and semantics, and if so, what aspects and processes exactly. We investigated how ALS patients understand verb phrases modified by temporal preposition phrases, e.g., ‘To watch TV for half an hour’. Interpretation here requires operations such as aspectual coercion that add or delete elements from event structures, depending on temporal modifiers, and constraints on coercion, which make combinations with certain modifiers not viable. Using a theoretically-motivated experimental design, we observed that acceptance rates for aspectual coercion were abnormally high in ALS patients. The effect was largest for the more complex cases of coercion: not those that involve enrichment of event structures (‘To switch on the TV in half an hour’, where a number of failed attempts must be included in the interpretation) but those that, if applied, would result in deletion of event structure elements (‘To repair the TV for half an hour’). Our experimental results are consistent with a deficit of constraints on coercion, and not with impaired semantic processes or representations, in line with recent studies suggesting that verb semantics is largely spared in ALS