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

Nusinersen treatment and cerebrospinal fluid neurofilaments : An explorative study on Spinal Muscular Atrophy type 3 patients

The antisense oligonucleotide Nusinersen has been recently licensed to treat spinal muscular atrophy (SMA). Since SMA type 3 is characterized by variable phenotype and milder progression, biomarkers of early treatment response are urgently needed. We investigated the cerebrospinal fluid (CSF) concentration of neurofilaments in SMA type 3 patients treated with Nusinersen as a potential biomarker of treatment efficacy. The concentration of phosphorylated neurofilaments heavy chain (pNfH) and light chain (NfL) in the CSF of SMA type 3 patients was evaluated before and after six months since the first Nusinersen administration, performed with commercially available enzyme-linked immunosorbent assay (ELISA) kits. Clinical evaluation of SMA patients was performed with standardized motor function scales. Baseline neurofilament levels in patients were comparable to controls, but significantly decreased after six months of treatment, while motor functions were only marginally ameliorated. No significant correlation was observed between the change in motor functions and that of neurofilaments over time. The reduction of neurofilament levels suggests a possible early biochemical effect of treatment on axonal degeneration, which may precede changes in motor performance. Our study mandates further investigations to assess neurofilaments as a marker of treatment response

Nusinersen safety and effects on motor function in adult spinal muscular atrophy type 2 and 3.

ABSTRACT Objective To retrospectively investigate safety and efficacy of nusinersen in a large cohort of adult Italian patients with spinal muscular atrophy (SMA). Methods Inclusion criteria were: (1) clinical and molecular diagnosis of SMA2 or SMA3; (2) nusinersen treatment started in adult age (>18 years); (3) clinical data available at least at baseline (T0-beginning of treatment) and 6 months (T6). Results We included 116 patients (13 SMA2 and 103 SMA3) with median age at first administration of 34 years (range 18–72). The Hammersmith Functional Rating Scale Expanded (HFMSE) in patients with SMA3 increased significantly from baseline to T6 (median change +1 point, p<0.0001), T10 (+2, p<0.0001) and T14 (+3, p<0.0001). HFMSE changes were independently significant in SMA3 sitter and walker subgroups. The Revised Upper Limb Module (RULM) in SMA3 significantly improved between T0 and T14 (median +0.5, p=0.012), with most of the benefit observed in sitters (+2, p=0.018). Conversely, patients with SMA2 had no significant changes of median HFMSE and RULM between T0 and the following time points, although a trend for improvement of RULM was observed in those with some residual baseline function. The rate of patients showing clinically meaningful improvements (as defined during clinical trials) increased from 53% to 69% from T6 to T14. Conclusions Our data provide further evidence of nusinersen safety and efficacy in adult SMA2 and SMA3, with the latter appearing to be cumulative over time. In patients with extremely advanced disease, effects on residual motor function are less clear

Can Intestinal Pseudo-Obstruction Drive Recurrent Stroke-Like Episodes in Late-Onset MELAS Syndrome? A Case Report and Review of the Literature

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a maternally inherited mitochondrial disorder that is most commonly caused by the m. 3243A>G mutation in the MT-TL1 mitochondrial DNA gene, resulting in impairment of mitochondrial energy metabolism. Although childhood is the typical age of onset, a small fraction (1-6%) of individuals manifest the disease after 40 years of age and usually have a less aggressive disease course. The clinicalmanifestations are variable and mainly depend on the degree of heteroplasmy in the patient's tissues and organs. They include muscle weakness, diabetes, lactic acidemia, gastrointestinal disturbances, and stroke-like episodes, which are the most commonly observed symptom. We describe the case of a 50-year-old male patient who presented with relapsing intestinal pseudo-obstruction (IPO) episodes, which led to a late diagnosis of MELAS. After diagnosis, he presented several stroke-like episodes in a short time period and developed a rapidly progressive cognitive decline, which unfortunately resulted in his death. We describe the variable clinical manifestations of MELAS syndrome in this atypical and relatively old patient, with a focus on paralytic ileus and stroke-like episodes; the first symptom may have driven the others, leading to a relentless decline. Moreover, we provide a brief revision of previous reports of IPO occurrence in MELAS patients with the m. 3243A>G mutation, and we investigate its relationship with stroke-like episodes. Our findings underscore the importance of recognizing gastrointestinal disturbance to prevent neurological comorbidities

TYMP Variants Result in Late-Onset Mitochondrial Myopathy With Altered Muscle Mitochondrial DNA Homeostasis

Biallelic TYMP variants result in the mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), a juvenile-onset disorder with progressive course and fatal outcome. Milder late-onset (>40 years) form has been rarely described. Gene panel sequencing in a cohort of 60 patients featuring muscle accumulation of mitochondrial DNA (mtDNA) deletions detected TYMP defects in three subjects (5%), two of them with symptom onset in the fifth decade. One of the patients only displayed ptosis and ophthalmoparesis. Biochemical and molecular studies supported the diagnosis. Screening of TYMP is recommended in adult patients with muscle mtDNA instability, even in the absence of cardinal MNGIE features

Diagnostic and prognostic value of CSF neurofilaments in a cohort of patients with motor neuron disease: A cross-sectional study

Motor neuron disease (MND) is a rare group of disorders characterized by degeneration of motor neurons (MNs). The most common form of MND, amyotrophic lateral sclerosis (ALS), is an incurable disease with a variable rate of progression. The search of robust biomarkers able to discriminate among different ALS forms is paramount to properly stratify patients, and to identify those who could most likely benefit from experimental therapies. Phosphorylated-neurofilament heavy chain (p-NfH) and neurofilament light chain (NfL) are neuron-specific components of the cytoskeleton and may represent reliable markers of neuronal injury in neurological disorders. In this study, we described our cohort of ALS patients in order to investigate whether and how cerebrospinal fluid (CSF) p-NfH and NfL levels may reflect progression rate, MN involvement and the extent of neurodegeneration. CSF p-NfH and NfL were significantly increased in ALS compared with healthy and disease controls, including patients with other forms of MND, and were higher in patients with more aggressive disease course, reflecting progression rate. We also evaluated neurofilament diagnostic accuracy in our centre, identifying with high sensitivity and 100% specificity cut-off values of 0.652 ng/mL for CSF p-NfH (P <.0001) and of 1261 pg/mL for NfL (P <.0001) in discriminating ALS from healthy controls. CSF neurofilaments were significantly correlated with ALS progression rate. Overall, CSF neurofilaments appear to reflect the burden of neurodegeneration in MND and represent reliable diagnostic and prognostic biomarkers in ALS