Intermediate conduction velocity in two cases of Charcot-Marie-Tooth disease type 1A.

BACKGROUND AND PURPOSE: Charcot-Marie-Tooth disease type 1A (CMT1A) is the most prevalent hereditary neuropathy worldwide and classically has slow nerve conduction velocity (NCV), in most cases below 38 m/s. Two unrelated patients with motor NCVs in the upper limbs above 38 m/s are reported. METHOD: Case report. RESULTS: Two genetically confirmed CMT1A patients are presented, from two unrelated families (one of British origin and the other of Brazilian origin). Both individuals had upper limb motor NCVs above 38 m/s, with values ranging from 41.9 to 45 m/s in the median nerve and from 42 to 42.3 m/s in the ulnar nerve. They presented with a very mild phenotype, with CMT Neuropathy Score version 2 (CMTNSv2) of 6 and 5, respectively. In contrast, affected family members within both kinships exhibited a classical phenotype with more severe disease manifestation (CMTNSv2 ranging from 12 to 20) and motor NCVs below 30 m/s. CONCLUSION: These cases, although very rare, highlight the importance of testing PMP22 duplication in patients with intermediate conduction velocities.

Primary neural leprosy: clinical, neurophysiological and pathological presentation and progression.

Disability in leprosy is a direct consequence of damage to the peripheral nervous system which is usually worse in patients with no skin manifestations, an underdiagnosed subtype of leprosy known as primary neural leprosy. We evaluated clinical, neurophysiological and laboratory findings of 164 patients with definite and probable primary neural leprosy diagnoses. To better understand the disease progression and to improve primary neural leprosy clinical recognition we compared the characteristics of patients with short (≤12 months) and long (>12 months) disease duration. Positive and negative symptoms mediated by small-fibres were frequent at presentation (∼95%), and symptoms tend to manifest first in the upper limbs (∼68%). There is a consistent phenotypic variability between the aforementioned groups. Deep sensory modalities were spared in patients evaluated within the first 12 months of the disease, and were only affected in patients with longer disease duration (∼12%). Deep tendon reflexes abnormalities were most frequent in patients with longer disease duration (P < 0.001), as well as motor deficits (P = 0.002). Damage to large fibres (sensory and motor) is a latter event in primary neural leprosy. Grade-2 disability and nerve thickening was also more frequent in cases with long disease duration (P < 0.001). Primary neural leprosy progresses over time and there is a marked difference in clinical phenotype between patients with short and long disease duration. Patients assessed within the first 12 months of symptom onset had a non-length-dependent predominant small-fibre sensory neuropathy, whilst patients with chronic disease presented an asymmetrical all diameter sensory-motor neuropathy and patchily decreased/absent deep tendon reflexes.

Neurodevelopmental outcomes in a cohort of children with congenital Zika syndrome at 12 and 24 months of age.

BACKGROUND: Early child development is a critical stage of life that influences social, educational and health outcomes worldwide. A few years after Zika epidemic, families of children born with congenital Zika syndrome (CZS) continue to face uncertainties when it comes to the development of their children. The present study sought to analyse the developmental trajectories of a subset of children born with CZS in the first 24 months of life. METHODS: Thirty-five children with CZS were assessed with the Bayley-III Scales at 12 and 24 months of age from November 2016 to December 2018 in a rehabilitation centre in Brazil. Inclusion criteria included children with established diagnosis of CZS. Exclusion criteria included the presence of arthrogryposis, prematurity, irregular follow-up, clinical complications or other causes of microcephaly. Children born with CZS who evolved with cerebral palsy (CP) were classified according to the Gross Motor Function Classification System (GMFCS) at 2 years of age. RESULTS: At 12 months of age mean composite scores on the Bayley cognitive, communication and motor scores were 57.71 (SD 7.11), 57.94 (SD 14.34) and 49.26 (7.20), respectively. At 24 months of age, composite scores were 57.43 (SD 7.11), 53.60 (SD 12.29) and 48.83 (7.76). In addition, 31 (88.57%) out of 34 children diagnosed with CP were classified as GMFCS levels IV and V. CONCLUSION: Zika virus congenital infection is a risk factor for functional impairments across all developmental domains having a direct and substantial negative impact in early child development.

Interleukin-31 and soluble CD40L: new candidate serum biomarkers that predict therapeutic response in multiple sclerosis.

Multiple sclerosis (MS) is a chronic demyelinating autoimmune disease that affects the central nervous system (CNS), varying from relatively benign to severely disabling. Although the roles of several cytokines and chemokines in MS are well established, their roles in MS lesions and evolution remain a matter of debate. Soluble CD40L (sCD40L) is a ligand that induces lymphocyte proinflammatory activity by stimulating the activation and maturation of B cells, promoting isotype switching and affinity hypermutation. Circulating sCD40L levels reflect activation of the CD40-CD40L complex. The interaction between CD40 and CD40L is of fundamental importance, suggesting their role in MS pathogenesis. Interleukin-31 (IL-31) is a proinflammatory cytokine that plays a role in allergies, autoimmune diseases, and is a major factor in several chronic inflammatory diseases. IL-31 triggers the JAK-STAT pathway in several different cell types, to induce proliferation and tissue remodeling in fibroblasts, epithelial cells, and endothelial cells. Some studies have described a correlation between these two cytokines and decreased serum levels of sCD40L and IL-31 after MS treatment, accompanied by a lower inflammatory response. In this review, we emphasize the possible correlation and positive feedback between IL31 and sCD40L in the MS proinflammatory response. We also describe the justification for this hypothesis and whether it is possible to investigate these cytokines as biomarkers of MS.

Clinical and magnetic resonance imaging patterns of extensive Chikungunya virus-associated myelitis.

Chikungunya fever is an arbovirus infection transmitted by the same mosquito vector of dengue and Zika virus. Besides high fever, common clinical symptoms include articular pain and general malaise. Neurological involvement is unusual, but some patients may develop peripheral and central nervous system involvement, including meningoencephalitis, myelitis, Guillain-Barré syndrome, and acute disseminated encephalomyelitis. We present three cases of Chikungunya fever complicated with extensive myelitis. The spinal cord magnetic resonance imaging (MRI) pattern is characterized by multiple dotted-like and longitudinal hyperintense lesions, with contrast enhancement, mostly distributed in the peripheral regions of the spinal cord. It seems that these lesions are mostly located in the perivascular spaces (PVS), related or not to virus attack. Involvement of brain PVS can also be demonstrated, as shown in two of the cases described. Considering the MRI pattern, extensive spinal cord lesion should include Chikungunya as a differential diagnosis, especially during an outbreak.

Magnetic resonance imaging features of COVID-19-related cranial nerve lesions.

The complete features of the neurological complications of coronavirus disease 2019 (COVID-19) still need to be elucidated, including associated cranial nerve involvement. In the present study we describe cranial nerve lesions seen in magnetic resonance imaging (MRI) of six cases of confirmed COVID-19, involving the olfactory bulb, optic nerve, abducens nerve, and facial nerve. Cranial nerve involvement was associated with COVID-19, but whether by direct viral invasion or autoimmunity needs to be clarified. The development of neurological symptoms after initial respiratory symptoms and the absence of the virus in the cerebrospinal fluid (CSF) suggest the possibility of autoimmunity.

Charcot-Marie-Tooth disease: Genetic profile of patients from a large Brazilian neuromuscular reference center.

This study aimed to describe the clinical, genetic, and epidemiological features of Charcot-Marie-Tooth disease (CMT) in Brazilian patients from a tertiary center, and to compare our data with previously published findings. This retrospective observational study conducted between February 2015 and July 2020 evaluated 503 patients (94 families and 192 unrelated individuals), diagnosed with CMT. Clinical and neurophysiological data were obtained from electronic medical records and blood samples were used for genetic analyses. Multiplex ligation-dependent probe amplification was used to assess duplications/deletions in PMP22. Sanger sequencing of GJB1 was performed in cases of suspected demyelinating CMT. Targeted gene panel sequencing was used for the remaining negative demyelinating cases and all axonal CMT cases. The first decade of life was the most common period of disease onset. In all, 353 patients had demyelinating CMT, 39 had intermediate CMT, and 111 had axonal CMT. Pathogenic or likely pathogenic variants were identified in 197 index cases. The most common causative genes among probands were PMP22 (duplication) (n = 116, 58.88%), GJB1 (n = 23, 11.67%), MFN2 (n = 12, 6.09%), GDAP1 (n = 7, 3.55%), MPZ (n = 6, 3.05%), PMP22 (point mutation) (n = 6, 3.05%), NEFL (n = 3, 1.52%), SBF2 (n = 3, 1.52%), and SH3TC2 (n = 3, 1.52%). Other identified variants were ≤1% of index cases. This study provides further data on the frequency of CMT subtypes in a Brazilian clinical-based population and highlights the importance of rarer and previously undiagnosed variants in clinical practice.

Predictors of early seizure recurrence among elderly inpatients admitted to a tertiary center: A prospective cohort study.

PURPOSE: Early seizure recurrence is common among elderly inpatients and is related to increased morbidity and a longer length of hospital stay. There are few studies on the short-term outcomes of seizures in the elderly population. We aimed to identify the predictors of early seizure recurrence among elderly inpatients. METHODS: We prospectively enrolled patients aged 60 years and older from a tertiary center who had seizures that either led to their hospital admission or occurred during hospitalization. We analyzed the demographic and hospitalization data, characteristics and etiology of seizures, and neurological and clinical comorbidities. Kaplan-Meier analysis was performed to determine the 30-day cumulative recurrence rates. The logrank test was used to analyze the risk of seizure recurrence within 30 days after the index seizure. Multivariable logistic regression analysis was used to identify risk factors for the recurrence of seizures within 30 days. RESULTS: Overall, 109 patients (mean age: 75.9 ±â€¯9.6 years) were enrolled. The mean age at the first-ever seizure was 74 ±â€¯11.7 years. Unprovoked seizures occurred in 59.6% of the patients. Cerebrovascular disorders were the most prevalent etiology (52.3%). Early seizure recurrence, defined as within 30 days, occurred in 27.5% of patients. Multimorbidity was found in 95.4% of our inpatients (6.3 ±â€¯2.3 [95% confidence interval, 5.4-7.2]), and the number of comorbidities was higher among those who had seizure recurrence than that among those who did not have seizure recurrence (p = 0.02). The probability of seizure recurrence was similar among the subgroups of patients who experienced acute seizures versus unprovoked seizures (both p = 0.03), and seizure recurrence was associated with a longer length of hospital stay (p = 0.005) compared to that of patients who did not experience seizure recurrence. After multivariate analysis, sepsis (p = 0.011), psychiatric disorders (p = 0.032), and cardiac arrhythmias (p = 0.037) were identified as risk factors for early seizure recurrence. CONCLUSIONS: Higher multimorbidity and a longer length of stay were associated with early seizure recurrence; and sepsis, psychiatric disorders, and cardiac arrhythmias were independent risk factors for early seizure recurrence among elderly inpatients.

The genetic heterogeneity of hereditary transthyretin amyloidosis in a sample of the Brazilian population.

To present the genetic heterogeneity of a sample of the Brazilian population with transthyretin (TTR) mutations. This cohort study was descriptive and retrospective, and enrolled patients with peripheral neuropathy of unknown cause that were found to have a mutation in the TTR gene during the process of etiological investigation, between July 1997 to January 2016. Over the study period, 129 point mutations were identified in 448 tested patients, of whom 128 were of Brazilian origin. The TTR Val30Met mutation was identified in 116 patients (90.6%); while 7 (4.7%) patients had a pathogenic non-TTR mutation and 7 (4.7%) carried non-pathogenic mutations (4.7%). The four non-TTRMet30 pathogenic mutations were TTR Aps38Tyr; TTR Ile107Val; TTR Val71Ala; and TTR Val122Ile. In the non-pathogenic group, we only found two mutations, including TTR Gly6Ser and TTR Thr119Thr. Our study depicts a scenario of greater genetic heterogeneity among Brazilian hereditary transthyretin amyloidosis (hATTR) patients with familial amyloidotic polyneuropathy (FAP). We expect that this number will grow fast over a short period of time, due to increasing availability of genetic tests, increasing knowledge of the disease and the multivariate origin of our population.

Guillain-Barré syndrome and Zika virus outbreaks.

PURPOSE OF REVIEW: Arboviruses have been associated with central and peripheral nervous system injuries, in special the flaviviruses. Guillain-Barré syndrome (GBS), transverse myelitis, meningoencephalitis, ophthalmological manifestations, and other neurological complications have been recently associated to Zika virus (ZIKV) infection. In this review, we aim to analyze the epidemiological aspects, possible pathophysiology, and what we have learned about the clinical and laboratory findings, as well as treatment of patients with ZIKV-associated neurological complications. RECENT FINDINGS: In the last decades, case series have suggested a possible link between flaviviruses and development of GBS. Recently, large outbreaks of ZIKV infection in Asia and the Americas have led to an increased incidence of GBS in these territories. Rapidly, several case reports and case series have reported an increase of all clinical forms and electrophysiological patterns of GBS, also including cases with associated central nervous system involvement. Finally, cases suggestive of acute transient polyneuritis, as well as acute and progressive postinfectious neuropathies associated to ZIKV infection have been reported, questioning the usually implicated mechanisms of neuronal injury. SUMMARY: The recent ZIKV outbreaks have triggered the occurrence of a myriad of neurological manifestations likely associated to this arbovirosis, in special GBS and its variants.