Hepatitis E virus and neurologic disorders Kamar, Nassim; Bendall, Richard P; Peron, Jean Marie ...
Emerging infectious diseases,
02/2011, Letnik:
17, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Information about the spectrum of disease caused by hepatitis E virus (HEV) genotype 3 is emerging. During 2004-2009, at 2 hospitals in the United Kingdom and France, among 126 patients with locally ...acquired acute and chronic HEV genotype 3 infection, neurologic complications developed in 7 (5.5%): inflammatory polyradiculopathy (n = 3), Guillain-Barre syndrome (n = 1), bilateral brachial neuritis (n = 1), encephalitis (n = 1), and ataxia/proximal myopathy (n = 1). Three cases occurred in nonimmunocompromised patients with acute HEV infection, and 4 were in immunocompromised patients with chronic HEV infection. HEV RNA was detected in cerebrospinal fluid of all 4 patients with chronic HEV infection but not in that of 2 patients with acute HEV infection. Neurologic outcomes were complete resolution (n = 3), improvement with residual neurologic deficit (n = 3), and no improvement (n = 1). Neurologic disorders are an emerging extrahepatic manifestation of HEV infection.
Hepatitis E virus (HEV) is the first cause of viral hepatitis in the world. While the water-borne HEV genotypes 1 and 2 are found in developing countries, HEV genotypes 3 and 4 are endemic in ...developed countries due to the existence of animal reservoirs, especially swine. An HEV infection produces many extra-hepatic manifestations in addition to liver symptoms, especially neurological disorders. The most common are neuralgic amyotrophy or Parsonage-Turner syndrome, Guillain-Barré syndrome, myelitis, and encephalitis. The pathophysiology of the neurological injuries due to HEV remains uncertain. The immune response to the virus probably plays a role, but direct virus neurotropism could also contribute to the pathophysiology. This review describes the main neurological manifestations and their possible pathogenic mechanisms.
ANXA11 mutations have previously been discovered in amyotrophic lateral sclerosis (ALS) motor neuron disease. To confirm the contribution of ANXA11 mutations to ALS, a large exome data set obtained ...from 330 French patients, including 150 familial ALS index cases and 180 sporadic ALS cases, was analyzed, leading to the identification of 3 rare ANXA11 variants in 5 patients. The novel p.L254V variant was associated with early onset sporadic ALS. The novel p.D40Y mutation and the p.G38R variant concerned patients with predominant pyramidal tract involvement and cognitive decline. Neuropathologic findings in a p.G38R carrier associated the presence of ALS typical inclusions within the spinal cord, massive degeneration of the lateral tracts, and type A frontotemporal lobar degeneration. This mutant form of annexin A11 accumulated in various brain regions and in spinal cord motor neurons, although its stability was decreased in patients' lymphoblasts. Because most ANXA11 inclusions were not colocalized with transactive response DNA-binding protein 43 or p62 deposits, ANXA11 aggregation does not seem mandatory to trigger neurodegeneration with additional participants/partner proteins that could intervene.
•Novel ANXA11 mutations are responsible for ALS.•ANXA11 mutations can be associated with early onset ALS and FTD.•Mutant G38 R ANXA11 is unstable in patient lymphoblasts.•Mutant G38 R ANXA11 led to cytoplasmic inclusions in post-mortem tissue.
Small fiber neuropathies (SFN) induce pain and/or autonomic symptoms. The diagnosis of SFN poses a challenge because the role of skin biopsy as a reference method and of each neurophysiological test ...remain to be discussed. This study compares six methods evaluating small sensory and autonomic nerve fibers: skin biopsy, Quantitative Sensory Testing (QST), quantitative sweat measurement system (Q-Sweat), Laser Evoked Potentials (LEP), Electrochemical Skin Conductance (ESC) measurement and Autonomic CardioVascular Tests (ACVT).
This is a single center, retrospective study including patients tested for symptoms compatible with SFN between 2013 and 2016 using the afore-mentioned tests. Patients were ultimately classified according to the results and clinical features as "definite SFN," "possible SFN" or "no SFN." The sensitivity (Se) and specificity (Sp) of each test were calculated based on the final diagnosis and the best diagnostic strategy was then evaluated.
Two hundred and forty-five patients were enrolled (164 females (66.9%), age: 50.4 ± 15 years). The results are as follows: skin biopsy: Se = 58%, Sp = 91%; QST: Se = 72%, Sp = 39%; Q-Sweat: Se = 53%, Sp = 69%; LEP: Se = 66%, Sp = 89%; ESC: Se = 60%, Sp = 89%; Cardiovascular tests: Se = 15%, Sp = 99%. The combination of skin biopsy, LEP, QST and ESC has a Se of 90% and a Sp of 87%.
Our study outlines the benefits of combining skin biopsy, ESC, LEP and QST in the diagnosis of SFN.
Background: Atrial fibrillation (AF) commonly affects patients with cardiac amyloidosis (CA). Amyloid deposition within the left atrium may be responsible for the subtype of AF in either permanent or ...non-permanent form. The prognostic implications of AF and its clinical subtype according to the type of CA are still controversial in this population. This study sought to investigate the prevalence, incidence and prognostic implications of AF and the clinical subtype of AF (permanent or non-permanent) in patients with CA.
Methods: Two hundred and thirty-eight patients with CA and full medical records were retrospectively enrolled in the study: About 115 (48%) with light chain (AL) amyloidosis and 123 (52%) with transthyretin amyloidosis (ATTR). Patient's medical records were reviewed to establish baseline prevalence, incidence and impact on all-cause and cardiovascular mortality during follow-up of AF.
Results: One hundred and four (44%) patients had history of AF at the time of diagnosis: 62 (60%) permanent and 42 (40%) non-permanent. There were 30 (26%) and 74 (60%) patients with history of AF among patients with AL and ATTR (including 5 hereditary and 69 wild-type), respectively (p<.0001). During the follow-up, 48 new patients developed AF (29, 12 and 7 among patients with AL, wild-type ATTR and hereditary ATTR). After adjustment for age, survival was similar in patients with or without history of AF (HR 0.87 (95% CI, 0.60 to 1.27; p = .467). AF had no impact on cardiovascular mortality. Among the 152 patients with history of AF included in the whole study, there were 75 (49%) patients with permanent AF. After adjustment for age, survival was similar in patients with permanent and non-permanent AF: HR 1.29 (95% CI, 0.84 to 1.99; p = .251). The results were the same among patients with AL or wild-type amyloidosis. Subtype of AF had no impact on cardiovascular mortality.
Conclusions: AF is common in patients with CA. However, AF and clinical subtype of AF have no impact on all-cause mortality, whatever the type of amyloidosis.
Dry immersion is a ground-based experiment simulating the effects of weightlessness, and it is a model of acute symmetrical bilateral deafferentation. This exploratory study aimed to investigate the ...effects of three days of dry immersion (DI) on sensory thresholds and the functioning of lemniscal pathways, assessed by somatosensory evoked potentials (SEPs).
Twelve healthy male volunteers (32+/-4.8 years) participated in the study. Sensory thresholds and SEPs of the tibial nerve of both limbs were recorded before (D-1) and on the third day of dry immersion (D3).
Sensory thresholds significantly decreased on D3 (-20.75 +/-21.7%; z = -2.54; p = 0.0109 on the right side and -22.18+/-17.28%; z = -3.059; p = 0.002 on the left side). The amplitude of P40 responses did not differ between D-1 and D3. Latencies of all central responses until P30 were shortened on D3 (N21 right:-0.57+/-0.31; z = -3.06; p = 0.002; N21 left -0.83+/-0.53; z = -2.94; p = 0.003; P30 right: -1.26+/-1.42; z = -3.059; p = 0.002; P30 left: -1.11+/-1.55; z = -2.27; p = 0.02).
Three days of dry immersion can induce hyperexcitability of lemniscal pathways.
This may be explained by a change in the expression of membrane channels and/or medullar plasticity and/or hypersensitization of peripheral sensory receptors induced by this acute deafferentation. Additional studies are needed to further elucidate the mechanisms.
Neuromuscular disease and peripheral neuropathy may cause drop foot with or without evertor weakness. We developed a helical-shaped, non-articulated ankle-foot orthosis (AFO) to provide ...medial-lateral stability while allowing mobility, to improve gait capacity. Our aim was to evaluate the effect of the helical AFO (hAFO) on functional gait capacity (6-min walk test) in people with peripheral neuropathy or neuromuscular disease (NMD) causing unilateral drop foot and compare with a posterior leaf spring AFO (plsAFO). Secondary aims were to compare functional mobility, 3D kinematic and kinetic gait variables and satisfaction between the AFOs.
Single centre, randomised crossover trial from January to July 2017 in 20 individuals (14 with peripheral neuropathy and 6 with NMD, 12 females, mean age 55.6 years, SD 15.3); 10 wore the hAFO for the first week and 10 wore the plsAFO before switching for the second week. The 6-min walk test (6MWT), Timed Up and Go (TUG) test and 3D gait analysis were evaluated with the hAFO, the plsAFO and shoes only (noAFO) at inclusion and 1 week after wearing each orthosis. Satisfaction was evaluated with the Quebec user evaluation of satisfaction with assistive technology (QUEST).
Median interquartile range 6MWT distance was greater with the hAFO (444 m 79) than the plsAFO (389 m 135, P < 0.001, Hedge's g = 0.6) and noAFO (337 m 91, P < 0.001, g = 0.88). TUG time was shorter with the hAFO (8.1 s 2.8) than the plsAFO (9.5 s 2.6, P < 0.001, g = - 0.5) and noAFO (10.0 s 2.6), P < 0.001, g = - 0.6). The plsAFO limited plantarflexion during the loading response (plsAFO - 7.5 deg 6.0 vs. noAFO -13.0 deg 10.0, P = 0.0007, g = - 1.0) but the hAFO did not (- 11.0 deg 5.1 vs. noAFO, P = 0.05, g = - 0.5). Quasi-stiffness was lower for the hAFO than plsAFO (P = 0.009, g = - 0.7). The dimensionless eversion moment was higher (though not significantly) with the hAFO than noAFO. Neither orthosis reduced ankle power (P = 0.34). Median total QUEST score was higher for the hAFO (4.7 0.7) than the plsAFO (3.6 0.8) (P < 0.001, g = 1.9).
The helical orthosis significantly and considerably improved functional gait performance, did not limit ankle mobility, increased lateral stability, though not significantly, and was associated with greater patient satisfaction than the posterior leaf spring orthosis. Trial registration The trial began before registration was mandatory.
Niemann-Pick disease type C (NP-C) is a neurodegenerative lysosomal lipid storage disease caused by autosomal recessive mutations in the NPC1 or NPC2 genes. The clinical presentation and evolution of ...NP-C and the effect of miglustat treatment are described in the largest cohort of patients with adolescent/adult-onset NP-C studied to date.
Observational study based on clinical chart data from adult patients with NP-C (> 18 year old) diagnosed in France between 1990 and 2015. Retrospective data from patients at diagnosis, onset of miglustat therapy (if applicable), and last follow up were analysed.
In France, patients with an adolescent-adult neurological form constituted approximately 25% of all NP-C cases diagnosed during the study period. Forty-seven patients (46 with NP-C1 and one with NP-C2; 53% female) were included. Mean ± SD (range) ages at neurological onset and diagnosis were 23.9 ± 12.5 (8-56) years and 34 ± 13.5 (15-65) years, respectively. At presentation, patients mainly had 1) impaired gait due to cerebellar ataxia and/or dystonia, 2) and/or cognitive/behavioural manifestations, 3) and/or psychotic signs. Initially, almost half of patients had only one of the above three neuro-psychiatric manifestations. Vertical supranuclear gaze palsy, usually occurring without patient complaint, was only detected on careful clinical examination and was recorded in most patients (93%) at the time of diagnosis, several years after neurological onset. Thirty-seven patients (79%) received miglustat, among whom seventeen (46%) continued beyond 2 years (at last follow up) to a maximum of 9.8 years. Eight patients (22%) discontinued treatment early due to side effects (n = 3) or perceived lack of efficacy (n = 5).Miglustat treatment duration correlated significantly with reduced neurological worsening (p < 0.001). Treatment for≥2 years was associated with improved patient survival (p = 0.029). Good responses to miglustat were associated with less severe neurological disability at the start of miglustat treatment (p = 0.02).
The proportion of adolescent/adult-onset NP-C cases diagnosed in France increased 2.5-fold since 2009 compared with the 2000-2008 period due to improved awareness. Adolescent/adult-onset NP-C frequently presented initially with a non-specific isolated neuro-psychiatric manifestation (motor, cognitive or psychotic). Patients with less severe neurological disability responded better to miglustat therapy.
Molecular defects in type 1 facioscapulohumeral muscular dystrophy (FSHD) are caused by a heterozygous contraction of the D4Z4 repeat array from 1 to 10 repeat units (RUs) on 4q35. This study ...compared (1) the phenotype and severity of FSHD1 between patients carrying 6-8 vs. 9-10 RUs, (2) the amount of methylation in different D4Z4 regions between patients with FSHD1 with different clinical severity scores (CSS). This cross-sectional multicenter study was conducted to measure functional scales and for genetic analysis. Patients were classified into two categories according to RUs: Group 1, 6-8; Group 2, 9-10. Methylation analysis was performed in 27 patients. A total of 99 carriers of a contracted D4Z4 array were examined. No significant correlations between RUs and CSS (r = 0.04,
= 0.73) and any of the clinical outcome scales were observed between the two groups. Hypomethylation was significantly more pronounced in patients with high CSS (>3.5) than those with low CSS (<1.5) (in DR1 and 5P), indicating that the extent of hypomethylation might modulate disease severity. In Group 1, the disease severity is not strongly correlated with the allele size and is mostly correlated with the methylation of D4Z4 regions.
Atrial arrhythmia (AA) is common among patients with cardiac amyloidosis (CA), who have an increased risk of intracardiac thrombus. The aim of this study was to explore the prognostic impact of ...vitamin K-antagonists (VKA) and direct oral anticoagulants (DOAC) in patients with CA.
273 patients with CA and history of AA with long term anticoagulation-69 (25%) light chain amyloidosis (AL), 179 (66%) wild-type transthyretin amyloidosis (ATTRwt) and 25 (9%) variant transthyretin amyloidosis (ATTRv)-were retrospectively included between January 2012 and July 2020. 147 (54%) and 126 (46%) patients received VKA and DOAC, respectively. Patient receiving VKA were more likely to have AL with renal dysfunction, higher NT-proBNP and troponin levels. Patients with ATTRwt were more likely to receive DOAC therapy. There were more bleeding complications among patients with VKA (20 versus 10%;
= 0.013) but no difference for stroke events (4 vs. 2%;
= 0.223), as compared to patients with DOAC. A total of 124 (45%) patients met the primary endpoint of all-cause mortality: 96 (65%) and 28 (22%) among patients with VKAs and DOACs, respectively (
< 0.001). After multivariate analysis including age and renal function, VKA was no longer associated with all-cause mortality.
Among patients with CA and history of AA receiving oral anticoagulant, DOACs appear to be at least as effective and safe as VKAs.
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