NMDA receptor activation accelerates ischemic energy depletion in the hippocampal slice and the demonstration of a threshold for ischemic damage to protein synthesis

Energy depletion is a primary factor initiating ischemic damage to neurons. In a separate report, we demonstrated that in vitro ischemia inhibits protein synthesis in the CA1 pyramidal neurons of the hippocampal slice via a mechanism involving extracellular calcium and N-methyl-D-aspartate (NMDA) receptor activation during the ischemic episode. In this study, we tested whether these agents accelerated the ischemic energy depletion beyond tolerable levels. ATP and phosphocreatine (PCr) were measured immediately after different durations of in vitro ischemia in the presence or absence of calcium and the NMDA receptor antagonist ketamine. The results support the contention that extracellular calcium does not contribute to the ischemic energy depletion. NMDA receptor activation accelerates the fall in ATP and PCr, but only during the first 45 s of the ischemia. Using protein synthesis inhibition as a functional indicator of ischemic damage in the hippocampal slice, we demonstrated that greater than 2 min of ischemia is necessary to inhibit protein synthesis. Thus, this threshold duration of ischemia indicates that events occurring between 2 and 5 min ischemia result in a prolonged protein synthesis inhibition.     

Accumulation of methotrexate and methotrexate polyglutamates in lymphoblasts at diagnosis of childhood acute lymphoblastic leukemia: a pilot prognostic factor analysis

Lymphoblasts in bone marrow samples, obtained from 43 children with acute lymphoblastic leukemia at diagnosis, were incubated with 1.0 mumols/L [3H] methotrexate for 24 hours in vitro. Nonexchangeable methotrexate and methotrexate polyglutamates were separated and quantitated. Event-free survival at 5 years was 38% +/- 9% for all 43 patients (27 failures), and 44% +/- 10% for the 35 with non-T, non-B- cell acute lymphoblastic leukemia (20 failures). Of these 35 children, those whose lymphoblasts accumulated more than 100 pmol methotrexate and 500 pmol methotrexate polyglutamates per billion cells experienced better 5-year event-free survival than those whose lymphoblasts did not (65% +/- 12% v 22% +/- 9%, P = .010). This difference characterized "good-risk" patients who were female (P = .014), less than age 7 at diagnosis (P = .005), or had low initial white blood cell counts (less than 20 X 10(9)/L, P = .018). Findings were similar for the 43 children with acute lymphoblastic leukemia and for the "good-risk" children in this total group. Thus, the ability of lymphoblasts to accumulate methotrexate and form methotrexate polyglutamates may be important to the curative properties of current therapy of acute lymphoblastic leukemia in children, particularly for "good-risk" patients. In such patients, inherent rather than acquired drug resistance may be the initial event leading to treatment failure.     

Validation of HeadCount-2w for estimation of two-week heading: Comparison to daily reporting in adult amateur player

Objectives

To validate the HeadCount-2w questionnaire for estimation of 2-week soccer heading by comparison to daily electronic diary reporting over the same two-week period.

Episodic Paroxysmal Hemicrania: 3 New Cases and a Review of the Literature

SYNOPSIS
Episodic paroxysmal hemicrania (EPH) is a rare, benign disorder characterized by discrete bouts of hemicranial headaches separated by periods of pain-free remissions. EPH is frequently mistaken for episodic cluster headache because they have similar temporal profiles and clinical features. EPH is differentiated from cluster headaches by an increased frequency and a shorter duration of individual attacks. Establishing the diagnosis of EPH is important because of its unique response to treatment with indomethacin and not standard anti-cluster headache medications.     

Varicella‐zoster virus encephalomyelitis with a prominent demyelinating component

The histopathologic presentation of varicella‐zoster virus (VZV) infection of the central nervous system is varied and is not well understood. Here we report a case of VZV encephalomyelitis with prominent demyelinating pathology in a patient with a history of follicular lymphoma treated with allogeneic stem cell transplantation. The patient presented with waxing and waning bilateral limb weakness and mental status changes. MRI showed leptomeningeal, peripheral spinal cord and periventricular cerebral white matter lesions in the brain, and polymerase chain reaction on cerebrospinal fluid detected VZV DNA. The patient expired from developing atrial fibrillation that rapidly progressed to ventricular fibrillation 10 days after admission to our hospital. Autopsy revealed macrophage‐rich areas of demyelination in the spinal cord and cerebrum with relative preservation of axons associated with inclusion bodies and positive immunostaining for VZV. This case represents a rare example of VZV encephalomyelitis presenting with a predominantly demyelinating, “multiple sclerosis‐like” pathology. The clinical and histopathologic findings and relevant literature are presented and discussed.     

Transcranial magnetic simulation in the treatment of migraine

Transcranial magnetic stimulation (TMS) is a diagnostic and therapeutic modality that is being developed as both an acute and preventive treatment for migraine. TMS delivers a fluctuating magnetic field from the scalp surface to induce current in the subjacent cortex. Magnetic pulses are delivered one at a time in single-pulse TMS (sTMS) or as a train of pulses in repetitive TMS (rTMS). For most of its 30-year history, TMS has been delivered in clinical and research settings using large tabletop devices. Based on the theory that sTMS may disrupt cortical spreading depression, sTMS has been studied and shown to be effective as an acute treatment for migraine with aura. Subsequent work in animal models confirms that sTMS disrupts cortical spreading depression. To make outpatient self-treatment possible, a portable device has been developed for acute treatment of migraine with aura. Based on the theory that rTMS alters brain excitability and neurotransmitter activity, rTMS has been studied as a preventive migraine treatment. A small body of evidence suggests that rTMS may have a role, but further studies are needed. In this review, we summarize the data on TMS as a treatment of migraine, and we suggest directions for future research.     

Hairy cell leukemia and myelomatosis: chance association or clinical manifestations of the same B-cell disease spectrum

We describe three patients who had typical features of hairy cell leukemia (HCL) and multiple myeloma (MM) at the same time. In two, both diagnoses were made within a short period of time, and in the third, HCL had been present for 2 yr before the appearance of a paraprotein, bone lesions, and plasma-cell infiltrates established the diagnosis of MM. Although this association has not been previously reported, cases of HCL with osteolytic lesions or a paraprotein band have been described. The cases described may represent clinical manifestations of closely related disorders arising from divergent differentiation from a common B-cell precursor rather than a chance association.     

Lymphangiomas in children: MR imaging

Seventeen lymphangiomas in 15 patients were imaged with magnetic resonance (MR) to define the nature, extent, and anatomic relationships of these lesions. The MR and pathologic findings were then compared to determine the histologic basis for the signal-intensity characteristics of these lesions. The signal intensity of 13 lesions was similar to or slightly less than that of muscle on T1-weighted images and greater than that of fat on T2-weighted images. This appearance correlated with the presence of ectatic lymphatic channels containing clear fluid on histologic section. Four lymphangiomas had high signal intensity, approximately equal to that of fat, on T1-weighted images, reflecting the presence of clotted blood or small cystic spaces with a higher ratio of fat to fluid. Sixteen of 17 lesions had visible septations on MR images. The authors' experience suggests that most lymphangiomas have a characteristic appearance on MR images. The information obtained with MR imaging can help in providing a preoperative diagnosis, in planning surgical resection, and in defining recurrence.