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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. [ABSTRACT FROM AUTHOR]

Abstract: Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine whose expression has been found to be critical to the generation of the antigen-specific immune response. Recent studies suggested that MIF plays a role in the initiation and maintenance of allergic disease. The aim of this study was to investigate whether MIF is involved in the pathogenesis of zinc-allergic systemic contact dermatitis. A 49-year-old Japanese woman developed facial edema, blepharedema and pruritic edematous erythema with papules over the entire body. Based of the results of a metal patch test, drug lymphocyte stimulating test and drug challenge test, diagnosis of zinc-allergic systemic contact dermatitis was made. Serum MIF and TNF-α levels of the patient, 20 healthy controls and other 6 patients who showed positive reaction to metal patch test were measured by an ELISA. Moreover we examined MIF production of peripheral blood mononuclear cells (PBMCs) from our patient, 3 healthy controls and other 2 patients who showed positive reaction to metal patch test at various metal concentrations. The patient’s serum showed high MIF and TNF-α levels compared to healthy controls and other metal allergy patients. Furthermore, zinc stimulation of patient’s PBMC showed higher MIF and TNF-α secretion compared with healthy subjects. The MIF content of 2 patients with other metal allergy was not significantly increased after metal stimulation. Our data suggest that zinc in the peripheral blood of zinc-allergic patients induce PBMCs to produce increased MIF levels, which could lead to systemic contact dermatitis. [Copyright &y& Elsevier]

The diagnosis of lupus erythematosus panniculitis (LEP) may be very difficult in cases in which involvement of the subcutaneous fat is the only manifestation of the disease. The main differential diagnosis is subcutaneous panniculitis-like T-cell lymphoma (SPTCL).We performed a retrospective study reviewing the histopathologic features of 11 biopsy specimens from nine patients with LEP (M : F = 2 : 7; median age: 48 years; range: 20–71 years).Histopathologically, all biopsies revealed a lobular panniculitis, with concomitant septal involvement in 82% of them. Dermal changes included the presence of superficial and deep infiltrates (82%) and mucin deposition (73%). The majority of cases (73%) presented also some form of epidermal involvement. The subcutaneous infiltrate was composed of lymphocytes in all cases, admixed with plasma cells in 91% of cases. Lymphoid follicles with reactive germinal centers were detected in 45% of cases. Immunohistochemistry showed a predominance ofα/β-T-helper and cytotoxic lymphocytes in 80% of cases admixed with B lymphocytes. The polymerase chain reaction analysis of the T-cell receptor (TCR)-γ gene showed a polyclonal smear in all cases.Our study shows that the most useful histopathologic criteria for distinguishing LEP from SPTCL are the presence of involvement of the epidermis, lymphoid follicles with reactive germinal centers, mixed cell infiltrate with prominent plasma cells, clusters of B lymphocytes, and polyclonal TCR-γ gene rearrangement.Massone C, Kodama K, Salmhofer W, Abe R, Shimizu H, Parodi A, Kerl H, Cerroni L. Lupus erythematosus panniculitis (lupus profundus): Clinical, histopathological, and molecular analysis of nine cases. [ABSTRACT FROM AUTHOR]

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. [Copyright &y& Elsevier]

The article presents a case of a 70-year-old Japanese man who was diagnosed with papuloerythroderma of Ofuji associated with early gastric cancer. The patient's dermatological examination revealed that the widespread of erythroderma while his biopsy specimen revealed early intramucosal gastric cancer. The patient undergone endoscopic mucosal resection of gastric cancer wherein his eosinophil counts in peripheral blood decreased to normal level.

Background: The relative incidence of malignant lymphoma subtypes differs according to geographic location. This study investigated the epidemiology of cutaneous lymphoma subtypes in Japan and compared it with other countries. Methods: Sixty-two patients with cutaneous lymphoma attending the Department of Dermatology, National Hospital Organization Hokkaido Cancer Center were reviewed. The World Health Organization classification of hematopoietic and lymphoid malignancies was adopted. Results: Of the 62 patients, 31 had primary cutaneous lymphoma (PCL) and 31 had secondary cutaneous lymphoma (SCL). T- and natural killer (NK)-cell lymphoma accounted for 80% of PCL, of which, mycosis fungoides accounted for almost 35%. Of the 31 patients with secondary cutaneous lymphoma, 17 patients (54%) had T- and NK-cell lymphoma, including nine adult T-cell leukemia/lymphoma patients, and 14 patients (46%) had B-cell lymphoma, including 11 diffuse large B-cell lymphoma patients. The majority of patients with SCL and NK-cell lymphoma with primary or secondary skin lesions had a poor outcome. Conclusions: PCL in this study showed a similar incidence to that of other institutions in Japan, while also demonstrating different frequencies from that of other countries, suggesting that the relative frequency of different PCL subtypes differ according to geographical location, similar to previous reports of systemic malignant lymphoma. [ABSTRACT FROM AUTHOR]

We report on two sisters with a T8993G point mutation of mitochondrial DNA, and their hearing evaluation. Considering auditory function, hearing in the elder sister remains almost normal. However, in the younger sister, the auditory brainstem response (ABR) threshold has fluctuated remarkably during a 3-year follow-up. The threshold changes of ABR in the younger sister suggest that her hearing problems may well be caused by both cochlear nerves and retrocochlear lesions. Our experience is clinically important because there have been only a few reports on hearing evaluation in patients with a T8993G point mutation of mitochondrial DNA. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

The article presents two case studies. Topics discussed include a 3-year-old boy with normal development, had a history of an unbalanced diet since infancy, preferring white rice, thinly shredded eggs, commercially available hamburger steaks, and minced chicken, with no vegetables or fruit; and 3-year-old boy with autistic spectrum disorder (ASD), beginning at 1.5 years of age, his preference for white foods, such as white rice and bread, became obvious.

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 24 h (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. [ABSTRACT FROM AUTHOR]

Highlights: [•] We evaluated the reliability and validity of the FNS with 1171 Japanese parents. [•] The Japanese version of the FNS is an assessment tool with 34 items among four factors. [•] It could be used for families with school-age children; the original FNS is not used with this population. [•] It could be used without regard to type or degree of disability. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A letter to the editor that discusses novel ABCA12 mutations identified in two cases of non- bullous congenital ichthyosiform erythroderma associated with multiple skin malignant neoplasia is presented.

A letter to the editor is presented about the effect of mutation in the GJB2 gene encoding connexin26 on a patient with palmoplantar keratoderma, sensorineural hearing loss and knuckle pads.

Summary: 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). [Copyright &y& Elsevier]

Summary: 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. [Copyright &y& Elsevier]

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 ≈30&ThickSpace;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. [ABSTRACT FROM AUTHOR]

Summary: 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 50–75dB 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. [Copyright &y& Elsevier]

α-N-Acetylgalactosaminidase (α-NAGA) deficiency with angiokeratoma corporis diffusum (AKCD) is one of the lysosomal storage diseases. GalNAcα1-O-Ser/Thr (Tn) is theoretically deposited in lysosomes, but substances with attached galactose and neuraminic (sialic) acid (T and sialosyl Tn, respectively) are excreted in patients’ urine. In this study, in two Japanese cases we analyzed the material accumulated in lysosomes using immunoelectron microscopy with mouse antibodies to Tn, sialosyl Tn and T (Thomsen–Friedenreich) antigens in order to find out what substance(s) is really deposited in lysosomes. We found that only GalNAcα1-O-Ser/Thr (Tn) was actually accumulated in vacuolated lysosomes of vascular endothelial cells, eccrine sweat gland cells, fibroblasts and pericytes. Galactosylation and sialylation of Tn appears to occur in cells other than those in the skin. The results suggest that this disease is caused by a single enzyme deficiency. [Copyright &y& Elsevier]

A letter to the editor is presented in response to the article about a case report on the manifestations of precursor B-cell lymphoblastic lymphoma.

A letter to the editor is presented in response to the article "Large Subcutaneous Abscesses Caused by Mycobacterium Fortuittum Infection," by Reine Moriuchi, Ken Arita and Hideyuki Ujiie.