Persistent verbal and behavioral deficits after resection of the left supplementary motor area in epilepsy surgery

An 8-year-old boy underwent a resection for focal cortical dysplasia at the left supplementary motor area (SMA) for the treatment of intractable epilepsy. The manifestations of SMA syndrome, such as transient mutism and right hemiparesis, resolved within a few weeks. Verbal disfluency and impaired executive function, accompanied by impulsivity and distractibility, persisted for more than 12 months. The verbal and behavioral problems caused serious difficulties in the school life of the patient, until they became less evident at 18 months after surgery. Tractography performed 18 months after surgery revealed a defect in the subportion of fronto-parietal association fibers within the left superior longitudinal fascicles. Verbal influency can persist with unusually long duration after resection of SMA during childhood. Although not discernible on the routine neuroimaging, white matter damage beneath the SMA region could result in serious disabilities in executive function. These complications should be recognized for the prediction and assessment of deficits in children after surgical intervention involving this region.     

Cell‐type‐dependent action potentials and voltage‐gated currents in mouse fungiform taste buds

Taste receptor cells fire action potentials in response to taste substances to trigger non‐exocytotic neurotransmitter release in type II cells and exocytotic release in type III cells. We investigated possible differences between these action potentials fired by mouse taste receptor cells using in situ whole‐cell recordings, and subsequently we identified their cell types immunologically with cell‐type markers, an IP₃ receptor (IP₃R3) for type II cells and a SNARE protein (SNAP‐25) for type III cells. Cells not immunoreactive to these antibodies were examined as non‐IRCs. Here, we show that type II cells and type III cells fire action potentials using different ionic mechanisms, and that non‐IRCs also fire action potentials with either of the ionic mechanisms. The width of action potentials was significantly narrower and their afterhyperpolarization was deeper in type III cells than in type II cells. Na⁺ current density was similar in type II cells and type III cells, but it was significantly smaller in non‐IRCs than in the others. Although outwardly rectifying current density was similar between type II cells and type III cells, tetraethylammonium (TEA) preferentially suppressed the density in type III cells and the majority of non‐IRCs. Our mathematical model revealed that the shape of action potentials depended on the ratio of TEA‐sensitive current density and TEA‐insensitive current one. The action potentials of type II cells and type III cells under physiological conditions are discussed.     

Prolonged grief following the recent death of a daughter among mothers who experienced distal losses during the Khmer Rouge era: Validity of the prolonged grief construct in Cambodia

This study addressed the validity of the prolonged grief (PG) construct in a Cambodian context. Eighty mothers who lost a young adult daughter stemming from a crowd stampede incident during the annual water festival were interviewed at the six-month post-loss point along with a control group of similarly aged women who were not recently bereaved. Both groups were assessed for PG, PTSD, anxiety, and depression symptoms and well as for the number of distal losses experienced during the Khmer Rouge (KR) regime – knowing that all the women were old enough to have lived through the KR regime. Support for the discriminant validity of PG was shown in a factor analysis in which its core symptoms were distinguished from anxiety, depression, and PTSD symptoms. Also, support was found for its incremental validity as shown in the unique sensitivity of PG in distinguishing the two groups when controlling for the other symptoms. Lastly, a positive relationship was found between the number of distal deaths experienced during the KR regime and PG symptom severity among the group of recently bereaved mothers, providing support for the predictive validity of PG. Implications as well as study limitations are discussed.     

Methotrexate myelopathy with extensive transverse necrosis: Report of an autopsy case

The patient was a 70‐year‐old woman with lymphoplasmacytic lymphoma which showed a predominantly diffuse involvement of the bone marrow and kidney. Because atypical lymphocytes appeared in the cerebrospinal fluid, the intrathecal administration of methotrexate (MTX) and cytosine arabinoside (Ara‐C) was repeated several times. The patient developed flaccid paraplegia 8 months after the beginning of intrathecal administration, and died 4 months later. Autopsy demonstrated extensive transverse necrosis involving the lower thoracic cord and marked vacuolar degeneration of the white matter of the cervical, upper thoracic and lumbo‐sacral cord. Focal vacuolar degeneration of the white matter was also noted in the left parietal lobe. Although vacuolar degeneration of the white matter is a common feature in MTX myelopathy, extensive transverse necrosis is rare. In the present case, an overlapping of two mechanisms, that is, injury of vascular endothelial cells and the direct toxic effect of MTX and Ara‐C on the white matter, probably played a crucial role in the pathogenesis of severe myelopathy. Because severe myelopathy occurs infrequently, considering the large number of patients receiving the intrathecal administration of MTX, it is possible that a constitutional predisposition or abnormal sensitivity to MTX was involved in the pathogenesis in the present patient.     

“Gliomatosis encephali” as a novel category of brain tumors by the first autopsy case report of gliomatosis cerebelli

Gliomatosis cerebri is a rare diffuse glioma that is neither mass‐forming nor necrotic, and does not disrupt existing structures. Gliomatosis occurring in the cerebellum is known as gliomatosis cerebelli, and only three such cases examined by biopsy have been reported. Here we describe the first autopsy findings of a patient who was diagnosed as having gliomatosis in the cerebellum. Neuropathological examination identified the tumor cells as being positive for glial fibrillary acidic protein, vimentin and nestin, with atypical nuclei that were cashew‐nut‐ or dishcloth‐gourd‐shaped. These tumor cells were dense in the right cerebellum, but also spread broadly throughout the brain including the left cerebrum and optic nerve. Mitotic figures were frequently seen in the cerebellum, brain stem and cerebrum. Scherer's secondary structures were evident not only in the cerebellum but also the cerebrum. No necrosis, microvascular proliferation or destruction of anatomical structures was detected in the whole brain. Differences in the origin of the tumors of the gliomatoses cerbri and cerebelli suggests these tumors are different types of brain tumors. Thus the findings support that the gliomatosis cerebelli is a novel type of brain tumor classification. Furthermore, by the similarities of the histological features among the tumors, it appears appropriate to establish a novel category of “gliomatosis encephali” which includes both gliomatosis cerebri and gliomatosis cerebelli.     

Nuclear Notch3 Expression is Associated with Tumor Recurrence in Patients with Stage II and III Colorectal Cancer

Background

The importance of Notch signaling in colorectal cancer (CRC) tumorigenesis has been recently recognized. However, the significance of Notch3 expression and its association with Notch1 expression in CRC is unclear. In the present study, we investigated Notch1 and Notch3 expression in Stage II and III CRC to assess their association with clinicopathological characteristics.

Methods

The protein expression of Notch1 and Notch3 was examined using immunohistochemistry in 305 CRC specimens. Nuclear expression of Notch1 and Notch3 and their associations with clinicopathological characteristics and distant relapse-free survival (dRFS) were evaluated.

Results

Nuclear Notch1 was overexpressed in 37 % of specimen, and nuclear Notch3 in 38 %. Nuclear Notch3 expression correlated with tumor differentiation status (P = 0.0099). Nuclear expression of Notch1 and Notch3 was associated with tumor recurrence (P = 0.0311 and P = 0.0053, respectively). In multivariate analysis, nuclear Notch3 expression [hazard ratio (HR) = 1.71; 95 % confidence interval (CI), 1.06–2.78; P = 0.0271), lymph node metastasis, and venous involvement were independently correlated with dRFS. In subgroup analysis, nuclear Notch3 expression was strongly associated with dRFS in Stage II CRC (HR = 3.47; 95 % CI 1.44–9.22; P = 0.0055). Both nuclear Notch1 and Notch3 were positive in 67 specimens (22 %) and both were negative in 144 specimens (47 %). Coexpression of nuclear Notch1 and Notch3 had an additive effect toward poorer dRFS compared with a negative subtype (HR = 2.48; 95 % CI, 1.41–4.40; P = 0.0019).

Conclusions

Nuclear Notch3 expression might be a novel predictive marker for recurrence in Stage II and III CRC.     

Diagnostic criteria for atypical hemolytic uremic syndrome proposed by the joint committee of the Japanese society of nephrology and the Japan pediatric society

Atypical hemolytic uremic syndrome (aHUS) is rare and comprises the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Recently, abnormalities in the mechanisms underlying complement regulation have been focused upon as causes of aHUS. The prognosis for patients who present with aHUS is very poor, with the first aHUS attack being associated with a mortality rate of ~25 %, and with ~50 % of cases resulting in end-stage renal disease requiring dialysis. If treatment is delayed, there is a high risk of this syndrome progressing to renal failure. Therefore, we have developed diagnostic criteria for aHUS to enable its early diagnosis and to facilitate the timely initiation of appropriate treatment. We hope these diagnostic criteria will be disseminated to as many clinicians as possible and that they will be used widely.