A 44-year-old previously healthy woman developed acute myelitis in close temporal relationship with ChAdOx1 nCoV-19 vaccine first-dose administration. The neurological involvement was mainly sensory ...with neuroimaging showing two mono-metameric lesions involving the posterior and lateral cord at dorsal level. Significant improvement was promptly recorded with high-dose intravenous steroids, with complete recovery within one month.
The strict temporal relationship between vaccination and myelitis, together with the absence of clues pointing to alternative diagnoses, might suggest a conceivable role for anti-SARS-CoV-2 vaccine as immunological trigger, although a causal relationship has yet to be established and our preliminary observation suggests caution.
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•Vaccine-related autoimmunity has been an interesting and rather complex matter of debate for years.•Any adverse event can be defined as vaccine-induced if peculiar requirements are met i.e., temporal association, consistency, specificity and strength.•We report on a patient with an inflammatory myelopathy in close temporal relationship with the first-dose of ChAdOx1 nCoV-19 vaccine administration.•The short interval between the onset of symptoms and the vaccination might point to a non-specific immunological mechanism of bystander activation.•Our preliminary observation suggests caution and further confirmation in larger cohorts is needed.
Background The syndrome of transient Headache and Neurological Deficits with cerebrospinal fluid (CSF) Lymphocytosis (HaNDL) is classified among secondary headaches attributed to "non-infectious, ...inflammatory intracranial disease". Despite its classification among secondary headaches, the current definition of HaNDL does not contemplate a causal agent. Thus, the aetiology, as well as the pathogenesis of both the headache and the transient focal deficits, remains unknown. Case presentation We describe a 29-year-old healthy male developing episodes of thunderclap headaches associated with recurrence of hemiparesis/hemi-paraesthesia; CSF showed lymphocytosis 200/mm.sup.3 and increased albumin; brain MRI revealed widespread leptomeningeal enhancement and a non-enhancing, circular diffusion restriction in the splenium of corpus callosum. Screening for neurotropic pathogens detected Epstein-Barr (EBV) DNA in serum and CSF, interpreted as a primary EBV infection once the seroconversion of EBV nuclear antigen (EBNA) IgM to IgG was proven on follow-up. Transcranial Doppler detected, during headache, increased flow velocity in middle cerebral arteries, possibly indicating vasospasm. Oral nimodipine was administered, with prompt clinical recovery, resolution of CSF/MRI abnormalities, and normalization of flow velocities in middle cerebral arteries. Case-based review Although the definition of HaNDL does not contemplate a viral trigger or abnormal brain imaging, we found other literature cases of HaNDL associated with direct or indirect signs of CNS infection. Conclusions At least in a proportion of patients, a viral aetiology may have a role in HaNDL. Whatever the aetiology, we suggest that the pathogenic mechanism may rely on the (viral or other) agent ultimately triggering cerebral vasoconstriction, which would explain both focal symptoms and headache. Calcium channel blockers might be a therapeutic option. Keywords: RCVS reversible cerebral vasoconstriction, Nimodipine, Headache, Corpus callosum, EBV, HaNDL
Abstract Frailty is a common age-related clinical syndrome characterized by a decline in the function of multiple organ systems, increased vulnerability to stressors, and a huge socio-economic ...burden. Despite recent research efforts, the physiopathological mechanisms underlying frailty remain elusive and biomarkers able to predate its occurrence in the early stages are still lacking. Beyond its physical component, cognitive decline represents a critical domain of frailty associated with higher risk of adverse health outcomes. We measured by High-Performance Liquid Chromatography (HPLC) a pool of serum amino acids including L-glutamate, L-aspartate, glycine, and D-serine, as well as their precursors L-glutamine, L-asparagine, and L-serine in a cohort of elderly subjects encompassing the entire continuum from fitness to frailty. These amino acids are known to orchestrate excitatory and inhibitory neurotransmission, and in turn, to play a key role as intermediates of energy homeostasis and in liver, kidney, muscle, and immune system metabolism. To comprehensively assess frailty, we employed both the Edmonton Frail Scale (EFS), as a practical tool to capture the multidimensionality of frailty, and the frailty phenotype, as a measure of physical function. We found that D-serine and D-/Total serine ratio were independent predictors of EFS but not of physical frailty. Furthermore, higher levels of glycine, glycine/L-serine and D-/Total serine were associated with worse cognition and depressive symptoms in the frail group. These findings suggest that changes in peripheral glycine and serine enantiomers homeostasis may represent a novel biochemical correlate of frailty.
We recently described increased D- and L-serine concentrations in the striatum of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys, the post-mortem caudate-putamen of human ...Parkinson's disease (PD) brains and the cerebrospinal fluid (CSF) of de novo living PD patients. However, data regarding blood D- and L-serine levels in PD are scarce. Here, we investigated whether the serum profile of D- and L-serine, as well as the other glutamate N-methyl-D-aspartate ionotropic receptor (NMDAR)-related amino acids, (i) differs between PD patients and healthy controls (HC) and (ii) correlates with clinical-demographic features and levodopa equivalent daily dose (LEDD) in PD. Eighty-three consecutive PD patients and forty-one HC were enrolled. PD cohort underwent an extensive clinical characterization. Serum levels of D- and L-serine, L-glutamate, L-glutamine, L-aspartate, L-asparagine and glycine were determined using High Performance Liquid Chromatography.
In age- and sex-adjusted analyses, no differences emerged in the serum levels of D-serine, L-serine and other NMDAR-related amino acids between PD and HC. However, we found that D-serine and D−/Total serine ratio positively correlated with age in PD but not in HC, and also with PD age at onset. Moreover, we found that higher LEDD correlated with lower levels of D-serine and the other excitatory amino acids. Following these results, the addition of LEDD as covariate in the analyses disclosed a selective significant increase of D-serine in PD compared to HC (Δ ≈ 38%). Overall, these findings suggest that serum D-serine and D−/Total serine may represent a valuable biochemical signature of PD.
•Serum D-serine concentrations increase during aging in PD patients but not in HC.•D-serine level directly correlates with age at PD onset.•Antiparkinsonian drugs downregulate D-serine and other NMDAR-stimulating aminoacids.•D-serine levels are affected by PD diagnosis and sex.
RAB39B pathogenic variants cause X-linked Parkinsonism associated with Intellectual Disability, known as Waisman syndrome, a very rare disorder that has been mainly identified through exome ...sequencing in large Parkinson's disease cohorts.
In this study we searched for pathogenic variants in RAB39B in two Italian families affected by X-linked early-onset Parkinsonism and Intellectual Disability.
Three patients received neurological evaluation and underwent RAB39B sequencing.
Two novel RAB39B frameshift variants were found to result in the absence of RAB39B protein (family 1: c.137dupT; family 2: c.371delA). Patients showed unilateral rest tremor and bradykinesia; one of them also displayed an early-onset postural tremor. Paramagnetic substance deposition in the substantia nigra, globus pallidi, red nucleus, putamen and pulvinar was assessed by brain imaging. Two patients also showed moderate calcification of globus pallidi.
In this study we highlight the evidence that X-linked early-onset Parkinsonism associated with Intellectual Disability occurs as a pattern of clinical and neuroimaging features attributable to RAB39B pathogenic variants.
•Loss of RAB39B may lead to X-linked Parkinsonism with Intellectual Disability.•Two novel RAB39B frameshift variants result in the absence of RAB39B protein.•We discuss the syndromic Parkinsonism's variable expression that may affect women.•We support the evidence that neuroimaging adds specific features to the syndrome.•RAB39B somatic mosaicism may be important for unravelling Parkinson's disease.
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