Herpes Simplex virus type 2 myeloradiculitis with a pure motor presentationin a liver transplant recipient

In this case report, we describe the first PCR-confirmed case of HSV2 myeloradiculitis with a purely motor presentation, occurring in a 68-year-old liver transplant recipient. The patient reported ascending weakness with no sensory nor sphincteric symptoms, thereby resembling acute demyelinating inflammatory neuropathy, or Guillain-Barr\ue9 syndrome. HSV2 was detected in cerebrospinal fluid by PCR, and the patient was successfully treated with intravenous Acyclovir

Amyotrophic lateral sclerosis phenotypes significantly differ in terms of magnetic susceptibility properties of the precentral cortex

The aim of our study was to investigate whether the magnetic susceptibility varies according to the amyotrophic lateral sclerosis (ALS) phenotypes based on the predominance of upper motor neuron (UMN)/lower motor neuron (LMN) impairment. We retrospectively collected imaging and clinical data of 47 ALS patients (12 with UMN predominance (UMN-ALS), 16 with LMN predominance (LMN-ALS), and 19 with no clinically defined predominance (Np-ALS)). We further enrolled 23 healthy controls (HC) and 15 ALS mimics (ALS-Mim). These participants underwent brain 3-T magnetic resonance imaging (3-T MRI) with T1-weighted and gradient-echo multi-echo sequences. Automatic segmentation and quantitative susceptibility mapping (QSM) were performed. The skewness of the susceptibility values in the precentral cortex (SuscSKEW) was automatically computed, compared among the groups, and correlated to the clinical variables. The Kruskal-Wallis test showed significant differences in terms of SuscSKEW among groups (χ2(3) = 24.2, p < 0.001), and pairwise tests showed that SuscSKEW was higher in UMN-ALS compared to those in LMN-ALS (p < 0.001), HC (p < 0.001), Np-ALS (p = 0.012), and ALS-Mim (p < 0.001). SuscSKEW was highly correlated with the Penn UMN score (Spearman's rho 0.612, p < 0.001). This study demonstrates that the clinical ALS phenotypes based on UMN/LMN sign predominance significantly differ in terms of magnetic susceptibility properties of the precentral cortex. Combined MRI-histopathology investigations are strongly encouraged to confirm whether this evidence is due to iron overload in UMN-ALS, unlike in LMN-ALS. • Magnetic susceptibility in the precentral cortex reflects the prevalence of UMN/LMN impairment in the clinical ALS phenotypes. • The degree of UMN/LMN impairment might be well described by the automatically derived measure of SuscSKEW in the precentral cortex. • Increased SuscSKEW in the precentral cortex is more relevant in UMN-ALS patients compared to those in Np-ALS and LMN-ALS patients

MYH2 myopathy, a new case expands the clinical and pathological spectrum of the recessive form

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Sexual Dimorphism in the Brain Correlates of Adult-Onset Depression: A Pilot Structural and Functional 3T MRI Study

Major Depressive Disorder (MDD) is a disabling illness affecting more than 5% of the elderly population. Higher female prevalence and sex-specific symptomatology have been observed, suggesting that biologically-determined dimensions might affect the disease onset and outcome. Rumination and executive dysfunction characterize adult-onset MDD, but sex differences in these domains and in the related brain mechanisms are still largely unexplored. The present pilot study aimed to explore any interactions between adult-onset MDD and sex on brain morphology and brain function during a Go/No-Go paradigm. We hypothesized to detect diagnosis by sex effects on brain regions involved in self-referential processes and cognitive control. Twenty-four subjects, 12 healthy (HC) (mean age 68.7 y, 7 females and 5 males) and 12 affected by adult-onset MDD (mean age 66.5 y, 5 females and 7 males), underwent clinical evaluations and a 3T magnetic resonance imaging (MRI) session. Diagnosis and diagnosis by sex effects were assessed on regional gray matter (GM) volumes and task-related functional MRI (fMRI) activations. The GM volume analyses showed diagnosis effects in left mid frontal cortex (p < 0.01), and diagnosis by sex effects in orbitofrontal, olfactory, and calcarine regions (p < 0.05). The Go/No-Go fMRI analyses showed MDD effects on fMRI activations in left precuneus and right lingual gyrus, and diagnosis by sex effects on fMRI activations in right parahippocampal gyrus and right calcarine cortex (p < 0.001, ≥ 40 voxels). Our exploratory results suggest the presence of sex-specific brain correlates of adult-onset MDD-especially in regions involved in attention processing and in the brain default mode-potentially supporting cognitive and symptom differences between sexes

A new case of limb girdle muscular dystrophy 2g in a greek patient, founder effect and review of the literature

Limb girdle muscular dystrophy (LGMD) type 2G is a rare form of muscle disease, described only in a few patients worldwide, caused by mutations in TCAP gene, encoding the protein telethonin. It is characterised by proximal limb muscle weakness associated with distal involvement of lower limbs, starting in the first or second decade of life. We describe the case of a 37-year-old woman of Greek origin, affected by disto-proximal lower limb weakness. No cardiac or respiratory involvement was detected. Muscle biopsy showed myopathic changes with type I fibre hypotrophy, cytoplasmic vacuoles, lipid overload, multiple central nuclei and fibre splittings; ultrastructural examination showed metabolic abnormalities. Next generation sequencing analysis detected a homozygous frameshift mutation in the TCAP gene (c.90_91del), previously described in one Turkish family. Immunostaining and Western blot analysis showed complete absence of telethonin. Interestingly, Single Nucleotide Polymorphism analysis of the 10 Mb genomic region containing the TCAP gene showed a shared homozygous haplotype of both the Greek and the Turkish patients, thus suggesting a possible founder effect of TCAP gene c.90_91del mutation in this part of the Mediterranean area. (C) 2018 Elsevier B.V. All rights reserved.Peer reviewe

CSF β-amyloid predicts prognosis in patients with multiple sclerosis

Background: The importance of predicting disease progression in multiple sclerosis (MS) has increasingly been recognised, hence reliable biomarkers are needed. Objectives: To investigate the prognostic role of cerebrospinal fluid (CSF) Amyloid beta1-42 (A) levels by the determination of a cut-off value to classify patients in slow and fast progressors. To evaluate possible association with white (WM) and grey matter (GM) damage at early disease stages. Methods: Sixty patients were recruited and followed-up for three to five years. Patients underwent clinical assessment, CSF analysis to determine Aβ levels, and brain MRI (at baseline and after 1 year). T1-weighted volumes were calculated. T2-weighted scans were used to quantify WM lesion loads. Results: Lower CSF Aβ levels were observed in patients with a worse follow-up EDSS (r=−0.65, p0.05). Conclusions: Low CSF Aβ levels may represent a predictive biomarker of disease progression in MS

Case report: A novel patient presenting TRIM32-related limb-girdle muscular dystrophy

Limb-girdle muscular dystrophy autosomal recessive 8 (LGMDR8) is a rare clinical manifestation caused by the presence of biallelic variants in the TRIM32 gene. We present the clinical, molecular, histopathological, and muscle magnetic resonance findings of a novel 63-years-old LGMDR8 patient of Italian origins, who went undiagnosed for 24 years. Clinical exome sequencing identified two TRIM32 missense variants, c.1181G &gt; A p.(Arg394His) and c.1781G &gt; A p.(Ser594Asp), located in the NHL1 and NHL4 structural domains, respectively, of the TRIM32 protein. We conducted a literature review of the clinical and instrumental data associated to the so far known 26 TRIM32 variants, carried biallelically by 53 LGMDR8 patients reported to date in 20 papers. Our proband's variants were previously identified only in three independent LGMDR8 patients in homozygosis, therefore our case is the first in literature to be described as compound heterozygous for such variants. Our report also provides additional data in support of their pathogenicity, since p.(Arg394His) is currently classified as a variant of uncertain significance, while p.(Ser594Asp) as likely pathogenic. Taken together, these findings might be useful to improve both the genetic counseling and the diagnostic accuracy of this rare neuromuscular condition

Stormorken syndrome caused by a p.R304W STIM1 mutation: The first Italian patient and a review of the literature

Stormorken syndrome is a rare autosomal dominant disease that is characterized by a complex phenotype that includes tubular aggregate myopathy (TAM), bleeding diathesis, hyposplenism, mild hypocalcemia and additional features, such as miosis and a mild intellectual disability (dyslexia). Stormorken syndrome is caused by autosomal dominant mutations in the STIM1 gene, which encodes an endoplasmic reticulum Ca2+ sensor. Here, we describe the clinical and molecular aspects of a 21-year-old Italian female with Stormorken syndrome. The STIM1 gene sequence identified a c.910C T transition in a STIM1 allele (p.R304W). The p.R304W mutation is a common mutation that is responsible for Stormorken syndrome and is hypothesized to cause a gain of function action associated with a rise in Ca2+ levels. A review of published STIM1 mutations (n = 50) and reported Stormorken patients (n = 11) indicated a genotype-phenotype correlation with mutations in a coiled coil cytoplasmic domain associated with complete Stormorken syndrome, and other pathological variants outside this region were more often linked to an incomplete phenotype. Our study describes the first Italian patient with Stormorken syndrome, contributes to the genotype/phenotype correlation and highlights the possibility of directly investigating the p.R304W mutation in the presence of a typical phenotype

Restless Sleep Disorder and the Role of Iron in Other Sleep-Related Movement Disorders and ADHD

In the last few years, restless sleep has been described as the key element of many clinical issues in childhood, leading to the recognition of “restless sleep disorder” (RSD) as a new proposed diagnostic category. The essential aid of video-polysomnographic recordings enables detection and quantification of the “large muscle group movements” (such as limb movements and repositioning) frequently described by parents of children with RSD. Strong evidence links iron deficiency to the pathophysiology of sleep-related movement disorders such as RSD, restless legs syndrome, periodic limb movement disorder, and attention deficit hyperactivity disorder (ADHD) due to the important role played by the brain dopamine production system. Serum ferritin is the main parameter used to evaluate iron deficiency in patients with sleep-related movement disorders. Iron supplementation is recommended when the serum ferritin level is <50 ng/mL, since the literature emphasizes the correlation between lower levels of serum ferritin, serum iron, and cerebrospinal fluid ferritin, and increased symptom severity. Moreover, several studies report an improvement in symptoms when ferritin levels are kept above 50 ng/mL. In this narrative review, we discuss the role of iron in sleep-related movement disorders, as well as ADHD, highlighting not only the connection between these two conditions, but also the relevance of iron supplementation for symptom improvement

Acute flaccid myelitis associated with enterovirus-D68 infection in an otherwise healthy child

Abstract Background Reporting new cases of enterovirus (EV)-D68-associated acute flaccid myelitis (AFM) is essential to understand how the virus causes neurological damage and to characterize EV-D68 strains associated with AFM. Case presentation A previously healthy 4-year-old boy presented with sudden weakness and limited mobility in his left arm. Two days earlier, he had an upper respiratory illness with mild fever. At admission, his physical examination showed that the child was febrile (38.5\ua0\ub0C) and alert but had a stiff neck and weakness in his left arm, which was hypotonic and areflexic. Cerebrospinal fluid (CSF) examination showed a mild increase in white blood cell count (80/mm 3 , 41% neutrophils) and a slightly elevated protein concentration (76 gm/dL). Bacterial culture and molecular biology tests for detecting viral infection in CSF were negative. The patient was then treated with intravenous ceftriaxone and acyclovir. Despite therapy, within 24\ua0h, the muscle weakness extended to all four limbs, which exhibited greatly reduced mobility. Due to his worsening clinical prognosis, the child was transferred to our Pediatric Intensive Care Unit; at admission he was diagnosed with acute flaccid paralysis of all four limbs. Brain magnetic resonance imaging (MRI) was negative, except for a focal signal alteration in the dorsal portion of the medulla oblongata, also involving the pontine tegmentum, whereas spine MRI showed an extensive signal alteration of the cervical and dorsal spinal cord reported as myelitis. Signal alteration was mainly localized in the central grey matter, most likely in the anterior horns. Molecular biology tests performed on nasopharyngeal aspirate and on bronchoalveolar lavage fluid were negative for bacteria but positive for EV-D68 clade B3. Plasmapheresis was performed and corticosteroids and intravenous immunoglobulins were administered. After 4\ua0weeks of treatment, the signs and symptoms of AFM were significantly reduced, although some weakness and tingling remained in the patient\u2019s four limbs. MRI acquired after 3\ua0weeks showed that the previously reported alterations were no longer present. Conclusion This case suggests that EV-D68 is a neurotropic agent that can cause AFM and strains are circulating in Europe. EV-D68 disease surveillance is required to better understand EV-D68 pathology and to compare various strains that cause AFM