Focal Coxsackie virus B5 encephalitis with synchronous seizure cluster and eruption: Infantile case.

Enterovirus focal encephalitis is a rare clinical entity that is characterized by focal neurological signs including seizure, hemiparesis, hemichorea, and headache, which are mainly followed by rapid spontaneous improvement. We herein describe the case of a 9-month-old boy who developed Coxsackie virus B5 (CVB5) focal encephalitis with seizure clusters in the eruption stage of roseola infantum-like illness, which were followed by rapid improvement and benign outcome. Lumbar puncture indicated pleocytosis, and CVB5 infection in the cerebrospinal fluid was subsequently identified on genome sequencing and virus isolation. Magnetic resonance imaging and electroencephalography showed no abnormal findings at the acute stage or on 2 month follow up. Although the pathogenesis of enterovirus focal encephalitis currently remains unclear, the pure synchronism of seizure cluster and eruption in this case suggests the involvement of local vascular impairment as the underlying pathogenesis.

[Study of the efficacy of low-dose synthetic ACTH therapy without tapering to treat West syndrome].

OBJECTIVE: We evaluated the effectiveness of synthetic adrenocorticotropic hormone (ACTH) therapy without tapering in treating patients with West syndrome. METHODS: Forty-four patients with cryptogenic (n = 7) or symptomatic (n = 37) West syndrome were treated with synthetic ACTH therapy between 2003 and 2012. The synthetic ACTH dosage was 0.0125 mg/kg/day administered daily for 2 weeks and then stopped without a tapering period. The initial effectiveness, long-term seizure outcome, and adverse effects were examined. RESULTS: During synthetic ACTH therapy, epileptic spasms disappeared in 37 of 44 patients (84.1%) and hypsarrhythmia on electroencephalography disappeared in 42 of 44 patients (95.5%). The average number of synthetic ACTH injections needed to achieve spasm control in these 37 patients was 5.8. Long-term seizure outcomes were assessed in 31 patients followed up for longer than half a year after synthetic ACTH therapy. Nine (29.0%) of these patients experienced recurrence of epileptic spasms, with a mean interval to recurrence of 2.4 months. Overall, 12 patients (38.7%) experienced various types of seizures other than spasms with a mean interval to recurrence of 8.0 months. Although adverse effects such as hypertension, infection, and mild brain shrinkage were noted in 13 patients (29.5%), no severe adverse effects were observed. CONCLUSIONS: These results are comparable to those of other reports on the initial effectiveness and long-term seizure control following synthetic ACTH therapy, and suggest that administration without tapering is reasonable to treat patients with West syndrome.

A case of early-infantile onset, rapidly progressive leukoencephalopathy with calcifications and cysts caused by biallelic SNORD118 variants.

Leukoencephalopathy with calcifications and cysts is a rare autosomal recessive genetic disorder neuroradiologically characterized by intracranial calcification, cerebral white matter disease, and multiple cysts. Although SNORD118 genes have recently been identified as a cause of this disorder, its clinical course varies for each patient. We report an early infantile case of this disease that progressed rapidly with confirmed SNORD118 variants. A 3-month-old female infant presented with epileptic seizures. Computed tomography revealed intracranial calcifications in the basal ganglia and thalamus. Magnetic resonance imaging demonstrated hyperintense lesions in the diffuse white matter on T2-weighted images starting at 7 months of age. Calcifications developed in the cerebral white matter, pons, and cerebellum. Small cysts appeared in the cerebral white matter at 1 year and 6 months. These cysts then began to increase bilaterally and expand rapidly. Although her epilepsy was controlled, she exhibited severe developmental delays and was unable to speak or walk at the age of 4 years. Whole-exome sequencing did not reveal any causal variants in the coding sequences. Further, Sanger sequencing revealed biallelic SNORD118 variants. Clinical features of this disease have not been established. To date, no cases with rapid changes in imaging results have been reported in detail prior to the appearance of cysts. Thus, we report a novel case that had an early infantile-onset and progressed rapidly with sequential appearance of calcification, white matter lesions and cysts. As SNORD118 variants might be missed by regular whole-exome sequencing, careful neuroimaging follow-up may be necessary to diagnose this disease.

Clinical effectiveness of efinaconazole 10% solution for treatment of onychomycosis with longitudinal spikes.

Onychomycosis with longitudinal spikes in the nail plate has been reported to be refractory to oral drugs as with dermatophytoma. We evaluated the efficacy of 10% efinaconazole solution in the treatment of onychomycosis with longitudinal spikes. Of the 223 subjects who were enrolled in a previous study, a post-hoc analysis of 82 subjects with longitudinal spikes was performed in this study. The opacity ratio of longitudinal spikes was decreased over time from 8.1 to 0.9 at the final assessment. In addition, the longitudinal spike disappearance rate increased early after the application to 81.7% at the final assessment. Therefore, 10% efinaconazole solution can be a first-line drug for longitudinal spikes, which have been regarded as refractory to oral drugs.

Potassium Bromide in the Treatment of Pediatric Refractory Epilepsy.

OBJECTIVE: We evaluated potassium bromide's (KBr's) efficacy and tolerability for pediatric refractory epilepsy. METHODS: We retrospectively reviewed the records of 42 patients treated with KBr in our hospital between 2008 and 2016 (age: 4 months to 19 years; mean: 6.2 years). Thirteen of them had 2 seizure types. The treatment durations ranged from 1 month to 6 years (mean: 15.0 months). RESULTS: KBr had an excellent effect (seizure-free status) in 3 patients (7.1%), a moderate effect (>50% reduction in seizure frequency from the pretreatment baseline) in 21 patients (50.0%), and no effect (<50% reduction in seizure frequency from the pretreatment baseline) in 18 patients (42.9%). The effective daily doses ranged from 20 to 80 mg/kg (mean: 50.0 mg/kg). KBr was effective in 59.1% patients with generalized epilepsy (n = 22), 55.6% patients with focal epilepsy (n = 18), and both patients with Dravet syndrome. An excellent or moderate effect was found in 72.2% patients with tonic seizures (n = 18), 66.6% patients with generalized tonic-clonic seizures (n = 6), 75.0% patients with secondary generalized seizures (n = 4), 46.2% patients with focal seizures (n = 13), and 20% patients with infantile spasms (n = 10) but no patients with myoclonic seizures (n = 2). Adverse effects including drowsiness, excitement, and rashes were reported in 13 patients (31.0%). CONCLUSIONS: These findings suggest that KBr is particularly effective for tonic seizures, generalized tonic-clonic seizures, and secondary generalized seizures. Although the adverse effects need further attention, KBr should be considered for pediatric refractory epilepsy.

Efficacy of long-term treatment with efinaconazole 10% solution in patients with onychomycosis, including severe cases: A multicenter, single-arm study.

We evaluated the efficacy of efinaconazole 10% topical solution in long-term use, for up to 72 weeks, for onychomycosis, including severe cases. Among 605 participants, 219 patients diagnosed as having onychomycosis were evaluated for the efficacy of efinaconazole. The treatment success rate (<10% clinical involvement of the target toenail) at the final assessment time point was 56.6%, the complete cure rate was 31.1% and the mycological cure rate was 61.6%, all of which increased over time, demonstrating that continuous application contributed to the improvement of cure rate. Even in severe cases, reduction of the affected nail area was observed, showing the potential efficacy of the treatment. Responses to a quality of life questionnaire among patients with onychomycosis, OnyCOE-t, suggested that efinaconazole treatment improved the patients' quality of life. The incidence of adverse drug reaction in the patients eligible for the assessment was 6.3%, and this developed only in the administration site in all cases. No systemic adverse event was observed. In addition, no increase in the incidence of adverse drug reaction due to long-term use was found. Efinaconazole therapy was proved to exhibit excellent balance between efficacy and safety, and thus may serve as a useful treatment option for onychomycosis.

Hearing profile and MRI myelination of auditory pathway in Pelizaeus-Merzbacher disease.

CONCLUSIONS: This study showed that delayed auditory pathway myelination is common in Pelizaeus-Merzbacher disease (PMD), but this delay does not necessarily indicate poor hearing function. OBJECTIVE: PMD is a rare recessively inherited X-linked leukodystrophy characterized by defective central nervous system myelination owing to a mutation in the proteolipid protein gene (PLP). The aims of this study were to evaluate the hearing function and auditory brain response (ABR) findings of patients with PMD and relate these findings to MRI-assessed myelination in the central auditory pathway. PATIENTS AND METHODS: We retrospectively studied eight male pediatric patients with PMD. Serial auditory examinations included audiometry, behavior audiometry, distortion product otoacoustic emission (DPOAE), and ABR. MRI-assessed myelination in the auditory pathway was evaluated in the PMD patients and in 23 normal young children as a control group. RESULTS: Audiometry showed normal to moderate hearing impairment and the hearing threshold improved with age and became almost normal over time. DPOAEs positivity and only ABR wave I or waves I and II were found in all the patients. MRI showed delayed myelination in all the patients and the auditory pathway was myelinated up to the inferior colliculus in four cases and up to the medial geniculate body in four cases. Serial MRIs showed no progression in myelination. No clear relation was found between hearing threshold and MRI-assessed myelination in the auditory pathway.

Feasibility and diagnostic agreement in teledermatopathology using a virtual slide system.

We investigated the feasibility and diagnostic agreement of a virtual slide system (VSS) in teledermatopathology. Forty-six biopsy specimens from inflammatory skin diseases were selected and scanned with a VSS at the Research Unit of Teledermatology, Medical University of Graz, Graz, Austria. Images were stored on a virtual slide server on which a specific Web application suited for telepathology (http://telederm.org/research/dermatopath/) runs. Twelve teleconsultants from 6 different countries reviewed the 46 cases, working directly on the Web application. Telediagnoses agreed with gold standard and conventional diagnosis with an average of 73% and 74%, respectively. Complete concordance among all teleconsultants with gold standard and conventional diagnosis was found in 20% of the cases. In 10 cases in which complete clinical data were missing, the average agreement of telediagnosis with gold standard diagnosis and conventional diagnosis decreased to 65% and 66%, respectively. Only 3 of 4 cases of inflammatory skin diseases were correctly diagnosed remotely with VSS. The system that we have used, despite its usability, is not completely feasible for teledermatopathology of inflammatory skin disease. Moreover, the performance seems to have been influenced by the availability of complete clinical data and by the intrinsic difficulty of the pathology of inflammatory skin diseases.

Ovarian teratoma development after anti-NMDA receptor encephalitis treatment.

BACKGROUND: Anti-NMDA-R receptor encephalitis occurs predominantly in younger women and is often comorbid with ovarian teratoma, a feature that is often absent in children. Here, we report our experience with two pediatric patients, in whom no tumors were present during treatment for encephalitis, but in whom ovarian teratomas developed without encephalitis relapse after treatment was completed. CASES: Patient 1 was a 14-year-old girl who was diagnosed due to characteristic symptoms and anti-NMDA-R antibody. MRI scanning during treatment revealed no ovarian tumors, but a tumor developed in the right ovary 10months after onset. Another tumor developed in the left ovary 3years after onset, and a mature ovarian teratoma was confirmed after bilateral partial ovariectomy. Patient 2 was an 11-year old girl who was also diagnosed due to characteristic symptoms and anti-NMDA-R antibody. Imaging during treatment revealed no ovarian tumors, but a 2.5-cm tumor mass was found in the left ovary 10months after onset, and a mature ovarian teratoma was confirmed after partial ovariectomy. DISCUSSION: This case report suggests the need for regular tumor screening after treatment for anti-NMDA receptor encephalitis because of potential subsequent tumor development, even in pediatric patients who initially present with no comorbid tumors. No analysis of relapse risk has yet been reported in cases of tumor development after treatment, and at this point, whether or not resection is needed to prevent relapse remains unclear. However, because teratomas usually grow, have an associated risk of torsion, and can be malignant, tumor removal should be considered.

A unique monoclonal antibody 29A stains the cytoplasm of amniotic epithelia and cutaneous basement membrane.

BACKGROUND: The basic function of epithelia is to provide a boundary between tissue and its external environment, and is achieved by a wide variety of components including extracellular molecules. Multiple monoclonal antibodies raised against epithelial antigens have helped identify a range of distinct, novel protein epitopes. OBJECT: In this study, we raised a monoclonal antibody to detect a novel epithelial molecular component. METHODS: We have produced a mouse monoclonal antibody using normal human amniotic tissue as an immunogen. The monoclonal antibody was subsequently immunohistochemically screened, and the target antigen was cloned using an immunoscreening method. RESULT: In the course of the screening, we identified unique antibody staining patterns within the cytoplasm of a subset of amniotic cells at intervals within the normal placental epithelia. By immunoscreening, we identified this candidate gene as laminin receptor (LR). By dot blot analysis, this antibody reacted with recombinant LR. The same localization of the antigen and LR was proved by a double staining immunofluorescence test in the placenta. This monoclonal antibody unexpectedly demonstrated linear staining within the dermal-epidermal junction of normal human skin but failed to react within the keratinocyte cytoplasm. CONCLUSION: We have produced and characterized a novel monoclonal antibody 29A that recognizes an LR-related molecule, which demonstrated a unique staining pattern. This monoclonal antibody might be a useful tool for further investigations into the epithelial tissues and the cutaneous basement membrane (BM).

Drugs indicated for mitochondrial dysfunction as treatments for acute encephalopathy with onset of febrile convulsive status epileptics.

We studied the efficacy of drugs indicated for mitochondrial dysfunction in the treatment of 21 patients with acute encephalopathy with onset of febrile convulsive status epilepticus at our hospital from January 2006 to December 2014. Among them, 11 patients had been treated with a mitochondrial drug cocktail consisting of vitamin B1, vitamin C, biotin, vitamin E, coenzyme Q10, and l-carnitine (prescription group) and 10 patients were not treated with the cocktail (non-prescription group). We retrospectively reviewed age, trigger, clinical form, treatment start time, and sequelae. Clinical form was classified into a biphasic group presenting acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and a monophasic group. Sequelae were classified as (A) no sequelae group or (B) sequelae group, and differences in the interval between diagnosis and treatment were also evaluated. The sequelae were not different between the mitochondrial drug cocktail prescription and non-prescription groups, but significantly better in the group administered the mitochondrial drug cocktail within 24h (P=0.035). We expect that early treatment with a mitochondrial drug cocktail could prevent sequelae in acute encephalopathy with onset of febrile convulsive status epilepticus.

Histopathologic features of early (patch) lesions of mycosis fungoides: a morphologic study on 745 biopsy specimens from 427 patients.

The histologic diagnosis of early mycosis fungoides (MF) is one of the most vexing problems in dermatopathology. We reviewed the histopathologic features of 745 biopsy specimens from 427 patients (male:female = 277:150; median age, 52 years; range, 3-95 years) with early (patch) lesions of MF collected from the lymphoma database of the Department of Dermatology of the Medical University of Graz (Austria). In all patients, the diagnosis was established by clinicopathologic correlation. The most common histopathologic pattern consisted of a band-like or patchy lichenoid infiltrate admixed with coarse bundles of collagen in the superficial dermis. Epidermotropism of lymphocytes was observed in most cases in one or more forms (single lymphocyte epidermotropism, 22%; basilar lymphocytes, 23%; Pautrier's microabscesses, 19%; "haloed" lymphocytes, 40%; disproportionate exocytosis, 17%; pagetoid epidermotropism, 3%). In 4% of cases, epidermotropism was completely missing. Atypical lymphocytes were present only in 9% of cases. Features of interface dermatitis were observed in 59% of cases. Other unusual findings were the presence of necrotic keratinocytes (23%), melanophages (8%), and extravasated erythrocytes (4%). In 28 patients, two or more biopsies taken on the same day at different body sites showed different histopathologic aspects, underlying the protean features of MF even in a single patient at a given time. Our study expands previous observations on histopathologic features of early lesions of MF. Although sometimes the histopathologic features are not diagnostic, they should be considered consistent with MF and do not rule out the diagnosis.

Treatment of lentigo maligna (melanoma in situ) with the immune response modifier imiquimod.

BACKGROUND: Surgical excision is the treatment of choice for lentigo maligna (LM), or melanoma in situ. Topical application of imiquimod, a local immune response modifier, is a novel therapeutic approach that leads to LM tumor clearance. This pilot, open-label, nonrandomized study evaluates the efficacy of imiquimod in patients with LM and other systemic problems that make them poor surgical risks. OBSERVATIONS: Six biopsy-proven cases of LM from 5 patients (age range, 67-80 years) in whom standard surgical therapy was contraindicated were enrolled in the study. Five tumors were located on the face and 1 on the right shoulder. Imiquimod was used as a 5% cream once a day for a maximum of 13 weeks. Immediate clinical responses and follow-up, as well as histopathologic changes and immunohistologic parameters (in 2 patients), were analyzed. The complete response rate for all LM cases was 100%. Time to complete clearing varied from 5 to 13 weeks based on both clinical and histopathologic findings. The inflammatory infiltrate following imiquimod treatment consisted of T-helper lymphocytes mixed with a significant number of cytotoxic cells and monocytes or macrophages. These results indicate that imiquimod induces a cytotoxic T-cell-mediated immune response. In all patients, erythema and erosions occurred at the treated area 2 to 4 weeks after initiation of imiquimod therapy. The patients have been followed up for 3 to 18 months without evidence of recurrences. CONCLUSIONS: Topical imiquimod appears to be an excellent therapeutic option for LM. Close evaluation of patients, including posttherapy histopathologic investigation, is essential. Imiquimod can be added to the list of therapeutic approaches for carefully selected patients with LM.

Papular mycosis fungoides: a new clinical variant of early mycosis fungoides.

BACKGROUND: Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma. In early stages of the disease many different clinicopathologic variants have been observed. OBSERVATION: We report 6 patients with early manifestations of MF characterized by the sole presence of papules which, unlike the papules of lymphomatoid papulosis, did not show a tendency for spontaneous resolution. Histologic examination confirmed the diagnosis of MF in all cases. Immunohistochemical staining for CD30 was negative in all cases. Follow-up data showed the nonaggressive behavior of the disease, confirming that the lesions were not manifestations of advanced MF. CONCLUSION: Papular MF is a new variant of early MF characterized by the presence of papules in the absence of more conventional early lesions (patches) of the disease. This variant should be added to the long list of clinicopathologic subtypes of MF.

Sensorineural hearing loss in patients with cerebral palsy after asphyxia and hyperbilirubinemia.

The location of lesions causing hearing loss in patients with cerebral palsy due to asphyxia or neonatal hyperbilirubinemia has remained unclear. We performed behavioral audiometry, distortion product otoacoustic emission (DPOAE) and auditory brainstem evoked response (ABR) in six patients with cerebral palsy due to asphyxia or neonatal hyperbilirubinemia in order to determine the lesion location causing their hearing impairment. In all cases, behavioral audiometry revealed a threshold elevation of 50-75 dB and ABR were no response. DPOAE were totally absent in five patients and normal in one patient. Our study suggests that lesions causing hearing loss potentially include the organ of Corti especially at the outer hair cells and the cochlear nerve.

A case of Mobius syndrome--radiological and electrophysiological findings.

Mobius syndrome is characterized by congenital bilateral facial palsy and abducens nerve paralysis, but reports of radiological and electrophysiological findings are scarce. A 4-year-old boy presented with mask-like facies noted at birth after a 34-week pregnancy. Examination revealed bilateral facial and abducens nerve paralysis with no other neurological abnormalities. Computed tomography revealed bilateral absence of facial nerve canal in the middle ear. Brain magnetic resonance imaging indicated a narrow than expected nerve in the internal auditory canal (IAC). Evoked electromyography and blink reflex testing to evaluate facial nerve function yielded no responses bilaterally. Facial palsy thus appears to be caused by facial nerve dysplasia or aplasia.

Three young adult patients with Pelizaeus-Merzbacher disease who showed only waves I and II in auditory brainstem responses but had good auditory perception.

Three young adult males with Pelizaeus-Merzbacher disease have been followed up since childhood. This disease is thought to be a dysmyelinating disorder of the brain during the prenatal period caused by gene mutations. The patients manifested horizontal nystagmus and severe rigidity of the extremities. Although the patients showed only waves I and II in auditory brainstem responses, they had relatively good hearing ability at approximately equal to dB. They could not speak words at all but could hear well and enjoy listening to conversation and music. One of them had a normal hearing threshold in pure-tone audiometry and a normal speech discrimination rate in speech audiometry. This can be explained by a nerve conduction blockade through dysmyelinated axons or the desynchronization of neurons and nerves responsible for the waves following waves I and II. At present, all three patients are living with their families. We report their present hearing, speech and language abilities.

The majority of keratinocytes incorporate intradermally injected plasmid DNA regardless of size but only a small proportion of cells can express the gene product.

The expression of intradermally injected DNA by keratinocytes is found mainly in the upper and middle layers of the epidermis. To investigate the mechanism of this selective expression, we observed the sequential changes in the distribution of interleukin-6-expressing keratinocytes after the introduction of the interleukin-6 gene. Transgene expression first occurred in basal keratinocytes and subsequently expanded to all epidermal layers and then remained in the upper layers. Semiquantitative analysis indicated that keratinocytes in the lower layers incorporated and lost DNA earlier than those in the upper layers. In order to examine the effect of the DNA size on the transgene expression, we constructed a plasmid containing a full-length 9 kb cDNA of type VII collagen and introduced it into keratinocytes. The expression pattern of type VII collagen in the epidermis was the same as those for smaller genes. This suggests that plasmid size has little or no effect on the expression pattern of the transfected gene. To trace the introduced plasmid, we intradermally injected a green fluorescence protein expression plasmid coupled with a rhodamine flag. Almost all keratinocytes in the injected areas showed rhodamine fluorescence. Furthermore, some cells also expressed green fluorescence protein. A lack of rhodamine fluorescence in the nucleus suggested an impairment of plasmid DNA transport from the cytoplasm to the nucleus. Collectively, our results show that the majority of keratinocytes take up the intradermally injected DNA regardless of its size, but that the transfer of DNA from the cytoplasm to the nucleus is limiting the transgene expression.

Diagnostic principles and new developments in primary cutaneous B-cell lymphomas.

The most common subtypes of primary cutaneous B-cell lymphomas are marginal zone B-cell lymphoma/immunocytoma, follicle center cell lymphoma, and large B-cell lymphoma of the leg. Precise classification (European Organization for Research and Treatment of Cancer (EORTC) scheme) can be achieved only after a complete synthesis of clinical, histopathological, immunophenotypic, and molecular features. It is extremely important to emphasize that primary cutaneous B-cell lymphomas differ significantly from their nodal counterparts and are frequently characterized by an excellent prognosis. Awareness of this special clinical behavior should prevent the application of unnecessarily aggressive treatment protocols. Future definitions of primary cutaneous B-cell lymphomas will be based on their etiology and pathogenesis and especially on their molecular features. Some important areas are presented where exciting findings have been detected.