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Neurotoxicology Jul 2021Konzo is a toxico-nutritional upper motor neuron disease causing a spastic paraparesis in schoolchildren and childbearing women in some African countries. Almost a...
Konzo is a toxico-nutritional upper motor neuron disease causing a spastic paraparesis in schoolchildren and childbearing women in some African countries. Almost a century since the first description of konzo, its underlying etiopathogenic mechanisms and causative agent remain unknown. This paper aims at refreshing the current knowledge of konzo determinants and pathogenesis in order to enlighten potential new research and management perspectives. Literature research was performed in PubMed and Web of Science databases according to the PRISMA methodology. Available data show that cassava-derived cyanide poisoning and protein malnutrition constitute two well-documented risk factors of konzo. However, observational studies have failed to demonstrate the causal relationship between konzo and cyanide poisoning. Thiocyanate, the current marker of choice of cyanide exposure, may underestimate the actual level of cyanide poisoning in konzo patients as a larger amount of cyanide is detoxified via other unusual pathways in the context of protein malnutrition characterizing these patients. Furthermore, the appearance of konzo may be the consequence of the interplay of several factors including cyanide metabolites, nutritional deficiencies, psycho-emotional and geo-environmental factors, resulting in pathophysiologic phenomena such as excitotoxicity or oxidative stress, responsible for neuronal damage that takes place at sparse cellular and/or subcellular levels.
Topics: Africa; Cyanides; Dietary Proteins; Humans; Malnutrition; Manihot; Motor Neuron Disease; Protein Deficiency; Risk Factors; Thiocyanates
PubMed: 33964344
DOI: 10.1016/j.neuro.2021.05.001 -
Journal of Neurochemistry Jul 2021To evaluate the neuroprotection exerted by ketosis against acute damage of the mammalian central nervous system (CNS). Search engines were interrogated to identify... (Meta-Analysis)
Meta-Analysis
To evaluate the neuroprotection exerted by ketosis against acute damage of the mammalian central nervous system (CNS). Search engines were interrogated to identify experimental studies comparing the mitigating effect of ketosis (intervention) versus non-ketosis (control) on acute CNS damage. Primary endpoint was a reduction in mortality. Secondary endpoints were a reduction in neuronal damage and dysfunction, and an 'aggregated advantage' (composite of all primary and secondary endpoints). Hedges' g was the effect measure. Subgroup analyses evaluated the modulatory effect of age, insult type, and injury site. Meta-regression evaluated timing, type, and magnitude of intervention as predictors of neuroprotection. The selected publications were 49 experimental murine studies (period 1979-2020). The intervention reduced mortality (g 2.45, SE 0.48, p < .01), neuronal damage (g 1.96, SE 0.23, p < .01) and dysfunction (g 0.99, SE 0.10, p < .01). Reduction of mortality was particularly pronounced in the adult subgroup (g 2.71, SE 0.57, p < .01). The aggregated advantage of ketosis was stronger in the pediatric (g 3.98, SE 0.71, p < .01), brain (g 1.96, SE 0.18, p < .01), and ischemic insult (g 2.20, SE 0.23, p < .01) subgroups. Only the magnitude of intervention was a predictor of neuroprotection (g 0.07, SE 0.03, p 0.01 per every mmol/L increase in ketone levels). Ketosis exerts a potent neuroprotection against acute damage to the mammalian CNS in terms of reduction of mortality, of neuronal damage and dysfunction. Hematic levels of ketones are directly proportional to the effect size of neuroprotection.
Topics: Animals; Brain Injuries, Traumatic; Central Nervous System Diseases; Diet, Ketogenic; Humans; Ketosis; Neuroprotection
PubMed: 33675563
DOI: 10.1111/jnc.15341 -
Pathogens (Basel, Switzerland) Feb 2021. Human T-cell lymphotropic virus type 1 (HTLV-1) is responsible for tropical spastic paraparesis and HTLV-1-associated leukemia/lymphoma. The infection is endemic in...
. Human T-cell lymphotropic virus type 1 (HTLV-1) is responsible for tropical spastic paraparesis and HTLV-1-associated leukemia/lymphoma. The infection is endemic in some areas of Peru, but its prevalence in the Peruvian Amazon is not well established. We aimed to assess the seroprevalence of HTLV-1 infection in pregnant women in the Peruvian Amazon. Moreover, we performed a systematic literature review and meta-analysis of the seroprevalence of HTLV infection in Peru. . This is a prospective cross-sectional study involving pregnant women attending health centers in the city of Iquitos, Peru, in May and June 2019. The presence of antibodies against HTLV-1 was assessed using ELISA (HTLV I + II ELISA recombinant v.4.0, Wiener lab, Rosario, Argentina). Positive cases were confirmed by Western Blot and HTLV-1 proviral load. . The study included 300 pregnant women with a mean age of 26 years (standard deviation [SD] 6.4). Five patients were diagnosed with HTLV-1 infection (prevalence 1.7%, 95% confidence interval (CI) 0.7% to 3.8%). Pregnant women with HTLV-1 infection were discretely younger (mean age 22.6 [SD 22.6] vs 26.8 [SD 6.3]; = 0.128). None of the five women had been transfused, and all were asymptomatic. Two (40%) also had a positive serology for , but larvae were not detected in any of the parasitological stool studies. The systematic review component identified 40 studies, which showed that the prevalence of infection in the general population was 2.9% (95% CI 1.2% to 5.3%) and in women of childbearing age, 2.5% (95% CI 1.2% to 4.0%). . The prevalence of HTLV-1 in the Peruvian Amazon basin is about 1.7%, indicating an endemic presence. Screening for HTLV-1 in prenatal care is warranted.
PubMed: 33668710
DOI: 10.3390/pathogens10030260 -
Neurology(R) Neuroimmunology &... May 2021To define the characteristics and the outcome of myelitis associated with immune checkpoint inhibitors (ICIs).
OBJECTIVE
To define the characteristics and the outcome of myelitis associated with immune checkpoint inhibitors (ICIs).
METHODS
We performed a retrospective research in the databases of the French Pharmacovigilance Agency and the OncoNeuroTox network for patients who developed myelitis following treatment with ICIs (2011-2020). A systematic review of the literature was performed to identify similar cases.
RESULTS
We identified 7 patients who developed myelitis after treatment with ICIs (anti-PD1 [n = 6], anti-PD1 + anti-CTLA4 [n = 1]). Neurologic symptoms included paraparesis (100%), sphincter dysfunction (86%), tactile/thermic sensory disturbances (71%), and proprioceptive ataxia (43%). At the peak of symptom severity, all patients were nonambulatory. MRI typically showed longitudinally extensive lesions, with patchy contrast enhancement. CSF invariably showed inflammatory findings. Five patients (71%) had clinical and/or paraclinical evidence of concomitant cerebral, meningeal, caudal roots, and/or peripheral nerve involvement. Despite the prompt discontinuation of ICIs and administration of high-dose glucocorticoids (n = 7), most patients needed second-line immune therapies (n = 5) because of poor recovery or early relapses. At last follow-up, only 3 patients had regained an ambulatory status (43%). Literature review identified 13 previously reported cases, showing similar clinical and paraclinical features. All patients discontinued ICIs and received high-dose glucocorticoids, with the addition of other immune therapies in 8. Clinical improvement was reported for 10 patients.
CONCLUSION
Myelitis is a rare but severe complication of ICIs that shows limited response to glucocorticoids. Considering the poor functional outcome associated with longitudinally extensive myelitis, strong and protracted immune therapy combinations are probably needed upfront to improve patient outcome and prevent early relapses.
Topics: Adolescent; Adult; Aged; Female; Glucocorticoids; Humans; Immune Checkpoint Inhibitors; Immunotherapy; Magnetic Resonance Imaging; Male; Middle Aged; Myelitis; Neoplasms; Retrospective Studies
PubMed: 33637598
DOI: 10.1212/NXI.0000000000000967 -
Viral Immunology 2021We aimed to verify the influence of intrinsic and extrinsic cell apoptotic pathways on the inhibition of cellular apoptosis in patients with tropical spastic...
We aimed to verify the influence of intrinsic and extrinsic cell apoptotic pathways on the inhibition of cellular apoptosis in patients with tropical spastic paralysis/myelopathy related to human T cell lymphotropic virus type 1. The databases accessed were PubMed, Scopus, Science Direct, and Web of Science. Neither the time of publishing nor the language of the articles was limited. The descriptors used for this systematic literature review were: Tropical Paraparesis, Proto-Oncogenic Protein C, Bcl-2, Bcl-X Protein, Bax protein, Fas ligand (FasL) protein, Fas receptor, TNF-related apoptosis-inducing ligand and Fas-associated protein with death domain (FADD)-like apoptosis regulating. The search resulted in 546 articles from which 9 articles were selected for analysis; ranging from serum levels of Bcl-2, Fas and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) measured by enzyme-linked immunosorbent assay and the levels of cellular expression of Bcl-2 and Bcl-xL the TCD4+ lymphocytes accessed by western blot. Most studies accessed either gene expression or polymorphism of Fas, FasL, and TRAIL in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), whereas one study used flow cytometry and fluorescence to determine Fas expression. Increased Bcl-xL expression inhibited T lymphocyte apoptosis, whereas Bcl-2, serum levels, and cellular expression did not influence T lymphocyte apoptosis and serum levels of Fas were significantly higher and associated with markers of leukocyte activation in patients with HAM/TSP. In addition, Fas polymorphism (FAS-670AA) was associated with higher proviral load. There is a need for additional research on this issue since the number of patients was small and the studies presented higher heterogeneity.
Topics: Apoptosis; Human T-lymphotropic virus 1; Humans; Paraparesis, Tropical Spastic
PubMed: 33470891
DOI: 10.1089/vim.2020.0131 -
International Journal of Surgery... Nov 2020Current treatment approaches for acute type B aortic dissection (TBAD) are diversified. Thoracic endovascular aortic repair (TEVAR) as an effective and convenient... (Comparative Study)
Comparative Study Meta-Analysis
Comparison of the efficacy and safety of thoracic endovascular aortic repair with open surgical repair and optimal medical therapy for acute type B aortic dissection: A systematic review and meta-analysis.
BACKGROUND
Current treatment approaches for acute type B aortic dissection (TBAD) are diversified. Thoracic endovascular aortic repair (TEVAR) as an effective and convenient intervention has been adopted extensively. However, the superior efficacy and safety of TEVAR have not yet been well evaluated. This meta-analysis was designed to comprehensively compare the efficacy and safety of TEVAR with open surgical repair and optimal medical therapy for acute type B aortic dissection.
METHODS
A systematic search of PubMed, Embase, Cochrane Library and Web of Science up to April 1, 2020 was conducted for relevant studies that compared the efficacy of TEVAR and other conventional interventions in the treatment of TBAD. The primary outcomes were early mortality and midterm or long term survival. The secondary outcomes included early complications and other late outcomes. Two reviewers assessed trial quality and extracted the data independently. All statistical analyses were performed using the standard statistical procedures provided in Review Manager 5.2.
RESULTS
A total of 18 studies including 12,789 patients were identified. 30-day/in-hospital mortality was significantly lower in TBAD patients with TEVAR than open surgical repair (OSR), with a pooled OR of 0.54 (95% CI 0.43-0.68; P < 0.00001). Compared with optimal medical therapy (OMT), TEVAR experienced lower incidence of long-term death (≥5-yr mortality), with a pooled OR of 0.46 (95% CI 0.24-0.86; P = 0.02). However, no significant difference between TEVAR and OSR or OMT in long-term survival was found. Compared with OSR, lower incidence of cardiac and pulmonary complications as well as shorter length of stay were observed in TEVAR. Compared with OMT, TEVAR showed higher rate of paraplegia or paraparesis, higher complete thrombosis of the false lumen, as well as longer length of ICU stay.
CONCLUSIONS
Our analysis shows that TEVAR may be favorable in reducing 30-day/in-hospital mortality (than OSR) and long-term mortality (than OMT). TEVAR experienced equal efficacy with OSR and OMT in long-term survival. TEVAR showed higher rate of paraplegia or paraparesis, higher complete thrombosis of the false lumen, as well as longer length of ICU stay than OMT; and lower incidence of cardiac and pulmonary complications as well as shorter length of stay than OSR. However, TEVAR indicated similar incidence of other complications and outcomes with OSR and OMT. Further studies especially randomized clinical trials are needed to comprehensively compare the efficacy TEVAR.
Topics: Adult; Aged; Aortic Dissection; Aorta, Thoracic; Aortic Aneurysm, Thoracic; Endovascular Procedures; Female; Hospital Mortality; Humans; Male; Middle Aged
PubMed: 32927144
DOI: 10.1016/j.ijsu.2020.08.051 -
Orthopedic Reviews Jun 2020Vertebral Hemangioma (VH) is a benign tumor usually symptomless and discovered incidentally. Pregnancy, because of several hormonal and physiologic changes, is a...
Vertebral Hemangioma (VH) is a benign tumor usually symptomless and discovered incidentally. Pregnancy, because of several hormonal and physiologic changes, is a recognized risk factor coinciding with the development of a rapid onset of neurological symptoms in patients affected by VH. In the Literature, sporadic cases of neurological symptoms have been described, which occurred during pregnancy, but only rarely the onset of symptoms was reported after pregnancy and childbirth. Usually surgical treatment is reserved for severe cases with rapid onset of neurological symptoms. However, the use of conservative treatments is still a topic of debate In the present study, we report a series of patients affected by VH become symptomatic during or after pregnancy along with a systematic review of the Literature.
PubMed: 32913613
DOI: 10.4081/or.2020.8685 -
World Neurosurgery Dec 2020Rosai-Dorfman disease (RDD) is a rare pathologic entity caused by sinus histiocytosis with massive cervical lymphadenopathy. Isolated spinal involvement is an infrequent...
BACKGROUND
Rosai-Dorfman disease (RDD) is a rare pathologic entity caused by sinus histiocytosis with massive cervical lymphadenopathy. Isolated spinal involvement is an infrequent presentation of extranodal RDD. The clinical and radiologic appearance of RDD represents a diagnostic challenge. We report 2 patients with paraparesis caused by RDD of the thoracic spine and a PRISMA-style systematic review.
CASE DESCRIPTION
There were 2 patients with isolated extranodal thoracic spinal RDD without cervical lymphadenopathy. One patient presented with anterior thoracic RDD and a subtotal resection. The small residual disease completely responded to the postoperative course of steroids. The second patient had extradural thoracic spine RDD, which was resected completely. A 6-month postoperative follow-up magnetic resonance imaging (MRI) scan showed local recurrence, which responded to radiation therapy. Five years follow-up of both patients showed normal neurologic functions and no recurrence on MRI scan surveillance.
CONCLUSIONS
RDD is a rare occurrence and should be considered in the differential diagnosis of extradural or intradural spinal lesions. Gross total resection is recommended, and long-term clinical follow-up with MRI is advised. Residual or recurrent RDD requires steroids or radiation therapy.
Topics: Adult; Female; Histiocytosis, Sinus; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Spinal Neoplasms; Steroids; Thoracic Vertebrae; Time Factors; Treatment Outcome
PubMed: 32827744
DOI: 10.1016/j.wneu.2020.08.097 -
Tropical Medicine & International... Nov 2019Human T-cell lymphotropic virus type 1 (HTLV-1), the causative agent of adult T-cell leukaemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Human T-cell lymphotropic virus type 1 (HTLV-1), the causative agent of adult T-cell leukaemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), is endemic in sub-Saharan Africa (SSA) and poses a high morbidity and mortality risk. Its prevalence in the general population is poorly understood. The potential for prevention motivated us to do a systematic review and meta-analysis of population-based studies to estimate the prevalence of HTLV-1 in SSA.
METHODS
A comprehensive, no-limit search was conducted in EMBASE, PubMed, Web of Science and the Cochrane Library from their inception dates to March 2019. Population-based studies presenting data on HTLV-1 in sub-Saharan Africa were included. Pooled prevalence was estimated using a random-effects meta-analysis.
RESULTS
A total of 21 studies were included, representing 42 297 participants. The pooled HTLV-1 seroprevalence was 3.19% (95% CI 2.36-4.12%) with variations across year of study. Prevalence of HTLV-1 positively correlated with year of study (β = 0.0036, P = 0.007). Participants from Central, Western and Southern Africa had a seroprevalence of 4.16% (95% CI 2.43-6.31%), 2.66% (95% CI 1.80-3.68%) and 1.56% (95% CI 0.48-3.15%), respectively.
CONCLUSIONS
Our findings suggest that HTLV-1 infection is a public health concern in SSA and highlight the need to implement effective preventive programmes and interventions aimed at reducing the burden of this common yet neglected infection.
Topics: Africa South of the Sahara; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Paraparesis, Tropical Spastic; Prevalence; Seroepidemiologic Studies
PubMed: 31465629
DOI: 10.1111/tmi.13305 -
Journal of Neurosurgery. Spine Aug 2019Spinal metastases from primary intracranial glioblastoma (GBM) are infrequently reported, and the disease has yet to be well characterized. A more accurate description... (Review)
Review
OBJECTIVE
Spinal metastases from primary intracranial glioblastoma (GBM) are infrequently reported, and the disease has yet to be well characterized. A more accurate description of its clinical presentation and patient survival may improve understanding of this pathology, guide patient care, and advocate for increased inclusion in GBM research. The authors sought to describe the clinical presentation, treatment patterns, and survival in patients with drop metastases secondary to primary intracranial GBM.
METHODS
A systematic review was performed using the PRISMA guidelines. PubMed/MEDLINE, Scopus, Web of Science, and Cochrane databases were queried for abstracts that included patients with primary intracranial GBM and metastases to the spinal axis. Descriptive statistics were used to evaluate characteristics of the primary brain lesion, timing of spinal metastases, clinical symptoms, anatomical location of the metastases, and survival and treatment parameters. Kaplan-Meier analysis and log-rank analysis of the survival curves were performed for selected subgroups.
RESULTS
Of 1225 abstracts that resulted from the search, 51 articles were selected, yielding 86 subjects. The patients' mean age was 46.78 years and 59.74% were male. The most common symptom was lumbago or cervicalgia (90.24%), and this was followed by paraparesis (86.00%). The actuarial median survival after the detection of spinal metastases was 2.8 months and the mean survival was 2.72 months (95% CI 2.59-4.85), with a 1-year cumulative survival probability of 2.7% (95% CI 0.51%-8.33%). A diagnosis of leptomeningeal disease, present in 53.54% of the patients, was correlated, and significantly worse survival was on log-rank analysis in patients with leptomeningeal disease (p = 0.0046; median survival 2.5 months [95% CI 2-3] vs 4.0 months [95% CI 2-6]).
CONCLUSIONS
This study established baseline characteristics of GBMs metastatic to the spinal axis. The prognosis is poor, though these results will provide patients and clinicians with more accurate survival estimates. The quality of studies reporting on this disease pathology is still limited. There is significant need for improved reporting methods for spinal metastases, either through enrollment of these patients in clinical trials or through increased granularity of coding for metastatic central nervous system diseases in cancer databases.
PubMed: 31374545
DOI: 10.3171/2019.5.SPINE19164