Molecular epidemiology of enteroviruses associated with severe hand, foot and mouth disease in Shenzhen, China, 2014-2018.

In this study, we investigated the epidemiology and molecular characteristics of enteroviruses associated with severe hand, foot and mouth disease (HFMD) in Shenzhen, China, during 2014-2018. A total of 137 fecal specimens from patients with severe HFMD were collected. Enterovirus (EV) types were determined using real-time reverse transcription polymerase chain reaction (RT-PCR), RT nested PCR, and sequencing. Sequences were analyzed using bioinformatics programs. Of 137 specimens tested, 97 (70.8%), 12 (8.8%), and 10 (7.3%) were positive for EV-A71, coxsackievirus A6 (CVA6), and CVA16, respectively. Other pathogens detected included CVA2 (2.9%, 4/137), CVA10 (2.9%, 4/137), CVA5 (0.7%, 1/137), echovirus 6 (E6) (0.7%, 1/137) and E18 (0.7%, 1/137). The most frequent complication in patients with proven EV infections was myoclonic jerk, followed by aseptic encephalitis, tachypnea, and vomiting. The frequencies of vomiting and abnormal eye movements were higher in EV-A71-infected patients than that in CVA6-infected or CVA16-infected patients. Molecular phylogeny based on the complete VP1 gene revealed no association between the subgenotype of the virus and disease severity. Nevertheless, 12 significant mutations that were likely to be associated with virulence or the clinical phenotype were observed in the 5'UTR, 2Apro, 2C, 3A, 3Dpol and 3'UTR of CVA6. Eight significant mutations were observed in the 5'UTR, 2B, 3A, 3Dpol and 3'UTR of CVA16, and 10 significant mutations were observed in the 5'UTR, VP1, 3A and 3Cpro of CVA10. In conclusion, EV-A71 is still the main pathogen causing severe HFMD, although other EV types can also cause severe complications. Potential virulence or phenotype-associated sites were identified in the genomes of CVA6, CVA16, and CVA10.

Occluso-facial manifestations in a child with the Rasmussen syndrome and intercurrent Lyme disease--a case report.

The Rasmussen Syndrome (RS) is a rare neurological disease, usually diagnosed in the 1st decade of life, leading to damage of the central nervous system. It is characterised by sudden seizures in previously healthy children. In this paper we present a case of a 14-year-old female patient with malocclusion who reported to the orthodontic clinic to start orthodontic treatment. The first symptoms of nervous system disorders manifested when the patient was 8 years old. Until then, the patient had been developing correctly. The interview revealed that at the age of 9 the patient was diagnosed with Lyme disease and a long-term antibiotics therapy was started. At the age of 10, the Rasmussen syndrome was diagnosed (the antibiotics therapy was discontinued) and confirmed by magnetic resonance imaging (MRI) and histopathological examination after brain biopsy. The study focuses in particular on the changes in the craniofacial skeleton and oral cavity, taking into account dynamically developing and increasing occlusion defects. The ethical aspect of the treatment has also been considered.

First Swedish case of fatal equine parasitic encephalitis by Halicephalobus gingivalis.

BACKGROUND: Halicephalobus gingivalis is a nematode with zoonotic potential which can cause fatal opportunistic infections in various mammals. The parasite has never been diagnosed in Sweden, in any species, prior to the presented case. CASE PRESENTATION: An imported 21-year-old Icelandic mare developed severe neurological signs. The horse was eventually euthanized and submitted for post-mortem examination where severe lesions in the kidneys were noted. Histopathology revealed the presence of H. gingivalis in both kidneys and the brain. Phylogenetic analysis of the parasite determined it to belong to Lineage 1. CONCLUSIONS: With the occurrence of H. gingivalis in Sweden, the disease should be added to the list of differential diagnoses in cases with acute onset of neurological disease in both horses and other mammals including humans.

Clinical Reasoning: A 43-Year-Old Man With Subacute Onset of Vision Disturbances, Jaw Spasms, and Balance and Sleep Difficulties.

A brainstem syndrome is recognizable in patients presenting with a combination of visual disturbances, incoordination, gait problems, speech and swallowing difficulties, and new-onset sleep symptomatology. Brainstem disorders of subacute onset (onset and progression with accumulation of disabling deficits in 6-12 weeks) are generally of autoimmune, infectious, inflammatory, or infiltrative neoplastic cause. An autoimmune or infectious brainstem disorder may be referred to as brainstem encephalitis or rhombencephalitis. We describe a patient with paraneoplastic autoimmune rhombencephalitis, in whom diagnostic clues included the following: diverse visual and sleep symptoms, trismus, and choking in the history; see-saw nystagmus, opsoclonus, dysarthria, jaw dystonia, and episodic laryngospasm on examination; subtle but longitudinal and nonenhancing T2 MRI abnormalities in the brainstem and upper cervical cord; and oligoclonal bands in the CSF. His movement disorder-specific neural IgG profile revealed ANNA-2 (anti-Ri) and KLHL-11-IgG. Both are biomarkers of paraneoplastic brainstem encephalitis. KLCHL-11-IgG has been reported to accompany germ cell tumors, which was found in a solitary metastasis to the left inguinal lymph node in our patient, along with an atrophic left testis. Multidisciplinary treatment (autoimmune neurology, sleep medicine, ophthalmology, and physiatry) led to significant clinical improvements. This case provides a framework for the evaluation of patients with subacute-onset brainstem syndromes and the investigation and management of those with paraneoplastic and other autoimmune diseases.

Cluster-like headache. A comprehensive reappraisal.

Among the primary headaches, cluster headache (CH) presents very particular features allowing a relatively easy diagnosis based on criteria listed in Chapter 3 of the International Classification of Headache Disorders (ICHD-II). However, as in all primary headaches, possible underlying causal conditions must be excluded to rule out a secondary cluster-like headache (CLH). The observation of some cases with clinical features mimicking primary CH, but of secondary origin, led us to perform an extended review of CLH reports in the literature. We identified 156 CLH cases published from 1975 to 2008. The more frequent pathologies in association with CLH were the vascular ones (38.5%, n = 57), followed by tumours (25.7%, n = 38) and inflammatory infectious diseases (13.5%, n = 20). Eighty were excluded from further analysis, because of inadequate information. The remaining 76 were divided into two groups: those that satisfied the ICHD-II diagnostic criteria for CH, 'fulfilling' group (F), n = 38; and those with a symptomatology in disagreement with one or more ICHD-II criteria, 'not fulfilling' group (NF), n = 38. Among the aims of this study was the possible identification of clinical features leading to the suspicion of a symptomatic origin. In the differential diagnosis with CH, red flags resulted both for F and NF, older age at onset; for NF, abnormal neurological/general examination (73.6%), duration (34.2%), frequency (15.8%) and localization (10.5%) of the attacks. We stress the fact that, on first observation, 50% of CLH presented as F cases, perfectly mimicking CH. Therefore, the importance of accurate, clinical evaluation and of neuroimaging cannot be overestimated.

Childhood Sjögren syndrome presenting as acute brainstem encephalitis.

Sjögren syndrome is an autoimmune disease characterized by dry mouth and eyes, known as sicca symptoms. The exact spectrum of neurological involvement, especially of the central nervous system, in childhood Sjögren syndrome has not been well defined. We report a girl who presented with acute febrile brainstem encephalitis. In retrospect, she had exhibited a preceding history of recurrent conjunctivitis and strong halitosis that could be considered as sicca symptoms. The histopathology results of a minor salivary biopsy, the presence of anti-SSA/Ro antibody, and keratoconjunctivitis confirmed the diagnosis of Sjögren syndrome. Commonly observed features in previously reported patients with childhood Sjögren syndrome and central nervous system complications have included fever at the time of neurologic presentation, cerebrospinal fluid pleocytosis, abnormal neuroimaging, and positivity for several specific antibodies. In children presenting with unknown acute febrile encephalopathy, Sjögren syndrome should be included in the differential diagnosis, especially when sicca symptoms are present.

ICAM-1 expression in autoimmune encephalitis visualized using magnetic resonance imaging.

The expression of leukocyte adhesion molecules in the intact brains of mice with experimental autoimmune encephalitis (EAE) was visualized by Magnetic Resonance Imaging (MRI) through the use of a new, target-specific MR contrast agent. Antibody-conjugated paramagnetic liposomes (ACPLs) were designed to achieve in vivo targeting of molecules expressed on vascular endothelium, while providing sufficient signal enhancement at these sites for detection by MRI. ACPLs targeted to intercellular adhesion molecule-1 (ICAM-1), an endothelial leukocyte receptor upregulated on cerebral microvasculature during EAE, were administered to diseased mice. Fluorescence microscopy confirmed that fluorescently-tagged ACPLs were localized to central nervous system (CNS) microvasculature in a pattern consistent with ICAM-1 upregulation described immunohistochemically. High resolution MRI of mouse brains ex vivo demonstrated that ACPL binding conferred significant enhancement of signal intensity (SI) as compared to control images. These results suggest that ACPLs can be used as MRI contrast agents to visualize specific molecules expressed on vascular endothelium during disease.

Ovine listerial encephalitis: analysis, hypothesis and synthesis.

Analysis of field data suggested that listerial encephalitis in sheep was most common in winter and early spring in the age groups of sheep which would be cutting, changing and possibly losing teeth. It was hypothesised that under these conditions ingested Listeria monocytogenes could reach the fine dental terminals of the trigeminal nerve causing an ascending neuritis and encephalitis. Experimental inoculation of organisms into the dental pulp demonstrated the feasibility of this route of infection. Histological encephalitis was evident six days after inoculation but the incubation period to clinical neurological disease was at least three weeks.

[Herpes paronychia]. / Die Herpes-Paronychie.

Herpetic whitlow is a rare viral infection, that should be treated nonoperatively and managed by a hand surgeon. There is a high risk of infection for dentists and other medical personal. The authors present a case, describe findings, possible complications, and treatment.

MRI characteristics of brainstem encephalitis in hand-foot-mouth disease induced by enterovirus type 71--will different MRI manifestations be helpful for prognosis?

The MRI characteristics of 21 HFMD patients with brainstem encephalitis resulting from EV71 infection were examined to identify lesion patterns helpful in disease classification and prognosis. The author reviewed the clinical and MRI data of 21 children with brainstem encephalitis infected during the EV71 outbreak in Hainan, China from May 2008 to September 2010. Thirteen cases of brainstem encephalitis were classified as type I based on unilateral or bilateral symmetrical patch-like hyperintense T1 and T2 MRI signals restricted to the posterior brainstem. In a significant minority of these cases (6/13), damage to the spinal ventral horn was also found. Among these 13 type I cases, 2 patients died, 7 recovered fully, and 4 suffered from various neurological sequelae. Eight cases were classified with type II brainstem encephalitis based on a vague, speckled hyperintense T1 and T2 signal pattern in the posterior brainstem. Six of these patients recovered fully, and 2 cases suffered from mild sequelae. Reexamination by MRI revealed an enduring lesion in only one type II case, restricted to the medulla oblongata. The prognosis of type II cases was better than that of type I cases. The lesion pattern revealed by MRI can distinguish type I from type II brainstem encephalitis due to EV71 infection and may prove valuable for prognosis. While lesions were usually located in the tegmental part of the brainstem in both patient groups, type I cases also demonstrated spinal, thalamic, and cortical lesions.

Oromandibular dystonia in encephalitis.

We report clinical and MRI findings of 17 patients with oromandibular dystonia (OMD) due to Japanese encephalitis (14) and nonspecific encephalitis (3). Their median age was 14(2-53) years and 9 were females. 8 patients had jaw open and 9 jaw close OMD. The severity ranged between 2 and 4 on a 0-4 scale, 11 patients were anarthric and needed tube feeding. Cranial MRI was abnormal in 13 patients; the abnormalities were in thalamus in 9, substantia nigra in 10, caudate in 3, globus pallidus and putamen in 2 each and pons in 1 patient. SPECT revealed hypoperfusion in thalamus in 4, basal ganglia in 1, frontal in 6, parietal in 3 and temporal in 1 patient. By 6 months, OMD regressed completely in 6, by 1 grade in 2 and remained unchanged in 7 patients. OMD in encephalitis is mainly due to JE and half of these patients improve.

Myeloencephalitis associated with a viridans group Streptococcus in a colony of Japanese macaques (Macaca fuscata).

Five weaned immature Japanese macaques (Macaca fuscata), bred in captivity, showed nervous signs over a 12-month period. Hemorrhagic cerebral infarcts with vasculitis were detected in four necropsied animals. The distribution and nature of the lesions were consistent with bacterial embolism, and a Streptococcus isolate, biochemically similar to S. salivarius, was recovered from the cerebral lesions from three of the four necropsied macaques. Treatment with antibacterial agents (enrofloxacin) improved the clinical condition of the surviving affected animal. These observations strongly suggest that this Streptococcus spp., member of the viridans group, is responsible for this outbreak. Dental pulpitis, present in two of the four macaques, probably served as the entry for this bacterium.

Clinical features and management of two cases of encephalitis lethargica.

Two patients with presumed encephalitis lethargica are presented with clinical features suggestive of two forms of the disease described by Von Economo: One patient had a psychosis and a mute-akinetic syndrome associated with myoclonus. The second patient presented with a psychosis and fever, developing severe dyskinesias involving the mouth, trunk and limbs, together with respiratory irregularities and presumed hypothalamic disturbance and disturbance of consciousness. In both cases, initial cerebrospinal fluid (CSF) examination revealed an elevated white cell count (predominantly lymphocytes), elevated protein in case 2, and oligoclonal bands in both cases. Computed tomography (CT) brain scan was normal but in both cases EEG revealed diffuse slow wave activity. A 18F-Dopa positron emission tomography (PET) scan in case 2 was normal. The medical management of both patients is discussed. In case 1, L-Dopa improved the akinesia, while the myoclonus responded to clonazepam. In case 2, the severe dyskinesias failed to respond to a number of drugs, and she ultimately required paralysis to relieve her almost continuous movements. Both patients responded rapidly and dramatically to intravenous methylprednisolone. We suggest that steroid treatment should be considered in the acute phase of patients with features suggestive of encephalitis lethargica.

Detection of viral DNA in neonatal herpes simplex virus infections: frequent and prolonged presence in serum and cerebrospinal fluid.

Polymerase chain reaction (PCR) assay was used to detect herpes simplex virus (HSV) DNA in mouth, skin, sera, or cerebrospinal fluid (CSF) from seven neonates with HSV infection. In a culture-negative patient, the diagnosis was confirmed by detection of HSV DNA. Serial examinations revealed that HSV DNA remained in the serum and/or CSF from several patients for 1-2 weeks after the beginning of treatment. Next, the results of PCR assay in neonatal HSV infections were compared with those in older children with herpes simplex encephalitis (HSE). HSV DNA was detected in CSF from four neonates with central nervous system involvement and in CSF from all nine children with HSE. Sera were positive for HSV DNA in five of seven neonates, including two cases of localized infections, but in none of the children with HSE. These results suggest that HSV may be spread principally via viremia in neonates. PCR assay could be useful for the confirmative diagnosis of neonatal HSV infections, especially in culture-negative cases.

Liposomes for targeted delivery of radioiodinated IVdU and 3-CH3-IVdU for non-invasive detection of herpes simplex virus encephalitis in mice.

Liposomal encapsulation of radioiodinated anti-herpes nucleosides was undertaken to reduce metabolic inactivation and increase blood-brain barrier penetration of the nucleosides, and so provide formulations suitable for use in the non-invasive scintigraphic diagnosis of herpes simplex encephalitis (HSE). The nucleosides investigated were [125I]-IVdU and its more lipophilic 3-methyl derivative, and they were encapsulated in phosphatidylcholine:cholesterol:sulfatide liposomes with an efficiency of 4.4% and 1.7% respectively. The encapsulation of IVdU reduced in vitro phosphorolysis (by 31% in serum at 25 degrees C over 3 hr as compared with non-encapsulated IVdU), and markedly increased in vivo stability (fifty-fold greater than that of free drug). In normal mice, higher radioactivity levels were observed in most tissues and there was prolonged, constant blood and brain uptake. Biodistribution of liposomal IVdU in herpes simplex virus (HSV) infected animals was similar, but somewhat lower concentrations were attained. Liposomal encapsulation of [125I]-3-CH3-IVdU produced less dramatic changes in tissue distribution in either healthy or HSV infected mice, as compared with the non-encapsulated drug. Whilst, in HSV infected mice, liposomal encapsulation of both drugs caused increased uptake by spleen, liver and lung, the uptake by brain was still too low for detection by whole-body scintigraphy.