The long-term effects of brief but repetitive febrile seizures (FS) on memory have not been as thoroughly investigated as the impact of single and prolonged seizure in the developing brain. Using a heated-air FS paradigm, we subjected male rat pups to one, three, or nine episodes of brief FS on days 10 to 12 postpartum. Neither hippocampal neuronal damage nor apoptosis was noted within 72 hours after FS, nor was there significant hippocampal neuronal loss, aberrant mossy fiber sprouting, or altered seizure threshold to pentylenetetrazol in any FS group at adulthood. The adult rats subjected to nine episodes of early-life FS, however, showed long-term memory deficits as assessed by the Morris water maze. They also exhibited impaired intermediate and long-term memory but spared short-term memory in the inhibitory avoidance task. Three hours after inhibitory avoidance training, phosphorylation of cAMP response-element binding (CREB) protein in the hippocampus was significantly lower in nine-FS-group rats than in controls. Furthermore, rolipram administration, which activated the cAMP-CREB signaling pathway by inhibiting phosphodiesterase type IV, reversed the long-term memory deficits in nine-FS-group rats by enhancing hippocampal CREB phosphorylation. These results raise concerns about the long-term cognitive consequences of even brief frequently repetitive FS during early brain development.

Reactive oxygen species (ROS) are implicated in reperfusion injury after focal cerebral ischemia (FCI). Reactive oxygen species regulate activity of transcription factors like NF-kappaB. The authors investigated the role of ROS in NF-kappaB activity after FCI using transgenic mice that overexpressed human copper/zinc-superoxide dismutase (SOD1) and that had reduced infarction volume after FCI. Superoxide dismutase transgenic and wild-type mice were subjected to 1 hour of middle cerebral artery occlusion (MCAO) and subsequent reperfusion. Immunohistochemistry showed SOD1 overexpression attenuated ischemia-induced NF-kappaB p65 immunoreactivity. Colocalization of NF-kappaB and the neuronal marker, microtubule-associated proteins (MAPs), showed that NF-kappaB was up-regulated in neurons after FCI. Electrophoretic mobility shift assays showed that SODI overexpression reduced ischemia-induced NF-kappaB DNA binding activity. Supershift assays showed that DNA-protein complexes contained p65 and p50 subunits. Immunoreactivity of c-myc, an NF-kappaB downstream gene, was increased in the ischemic cortex and colocalized with NF-kappaB. Western blotting showed that SOD1 overexpression reduced NF-kappaB and c-Myc protein levels in the ischemic brain. Colocalization of c-Myc and TUNEL staining was observed 24 hours after FCI. The current findings provide the first evidence that SOD1 overexpression attenuates activation of NF-kappaB after transient FCI in mice and that preventing this early activation may block expression of downstream deleterious genes like c-myc, thereby reducing ischemic damage.

Platelet activation was significantly increased in acute ischemic stroke and substantially decreased thereafter. The lesser long-term pharmacodynamic potency of aspirin relative to clopidogrel raises the prospect of the need for more effective antiplatelet agents or a synergistic combination therapy for stroke prevention in the future.

Summary:Purpose: Reversible cerebral vasoconstriction has been hypothesized to be the etiology of seizures due to hypercalcemia, but angiographic studies documenting vasoconstriction have not previously been available.Methods: We present a 43-year-old woman who had frequent seizures that later evolved to status epilepticus with marked hypercalcemia at the time of the seizures.Results: Magnetic resonance imaging (MRI) of the patient's brain revealed high signal changes in T 2 -weighted imaging, fluorescence-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging (DWI) over the bilateral occipital and thalamic areas. Cerebral angiography showed blood vessels narrowing, disappearing altogether over the right posterior cerebral artery (PCA) branch, which is compatible with vasoconstriction. Vasoconstriction caused the MRI high signal in the occipital area, which was associated with subsequent periodic lateralized epileptic discharges. The patient's clinical condition improved with management of seizures and hypercalcemia. A second brain MRI 2 weeks later revealed complete resolution of the high-signal lesions. Follow-up cerebral angiography study also showed total recovery of vasoconstriction.Conclusions: The sequence of events suggests the hypothesis that reversible cerebral vasoconstriction may play a role in hypercalcemia-induced seizures. Key Words: SeizureHypercalcemia-Vasoconstriction.Hypercalcemia can cause drowsiness, lethargy, weakness, confusion, and coma, but rarely causes seizures. Neuronal membrane excitability changes (1,2), hypertensive encephalopathy, and vasoconstriction induced by hypercalcemia all have been hypothesized to be the etiologies of seizures (1,3), but vasoconstriction during hypercalcemic seizures has not yet been reported. We present a patient with status epilepticus, caused by breast carcinoma-induced hypercalcemia. Serial brain magnetic resonance imaging (MRI) and cerebral angiography studies showed reversible occipital high-signal abnormalities and transient cerebral vasoconstriction. These findings suggest that vasoconstriction is a contributing factor to hypercalcemia-related seizures. CASE REPORTA 43-year-old right-handed housewife had low back pain and osteoporosis for several years. She was brought to the emergency room (ER) for frequent seizures. The paAccepted January 28, 2004. Address correspondence and reprint requests to Dr. S-L. Lai at Department of Neurology, Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, Taiwan, 123 Ta-Pei Rd. Niao-Sung Hsiang, Kaohsiung County, Kaohsiung, Taiwan. E-mail: carlos@adm.cgmh.org.tw tient was unconscious, and frequent partial seizures with secondary generalization were noted while she was in the ER. Laboratory evaluation disclosed severe hypercalcemia with serum total calcium of 15.5 mg/dl. Hydration with normal saline at 100 ml/h and magnesium sulfate were administered as treatment for hypercalcemia. Diazepam (DZP) and phenytoin (PHT) were given for the status epilepticus. Physical examination detected a left breast mass,...

Background: Immune checkpoint inhibitors (ICIs) have significantly changed the current approach to cancer treatment. Although the use of ICIs has become the standard of care for advanced melanoma, reports of ICI use among Asian populations with melanoma are limited. Therefore, we conducted this retrospective study to assess the efficacy and safety of ICI use in Taiwanese patients. Conclusion:ICIs demonstrated efficacy and safety in Taiwanese patients with melanoma. Combination treatment showed the greatest efficacy, but this was also accompanied by greater toxicity among the four regimens. In addition, we identified important prognostic factors, such as liver metastases, performance status, and tumor response, for both PFS and OS. These findings could provide physicians with more information to justify clinical outcomes observed in Asian patients with advanced melanoma.

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Background and Purpose: Spontaneous intracranial hypotension (SIH) is an uncommon, but not rare, cause of headache. We analyzed a series of patients with SIH and attempted to establish a clinical procedure. Methods: We retrospectively reviewed 11 patients with SIH who were admitted between January 2004 and May 2007. Data recorded from patients included basic data, clinical symptoms, neurological imaging studies and treatment. Results: Orthostatic headache was the most common symptom, but there were still 2 patients without orthostatic headache. Diffuse pachymeningeal enhancement was the most common finding in brain MRI study and engorgement of the spinal epidural venous plexus was the most common finding in spinal MRI study. Eight of our patients received epidural blood patches in the lumbar area and 6 of these were symptom-free within 2 weeks. Two patients received spinal MRI immediately after administering the epidural blood patch, and this revealed that most of the blood had spread to the upper cervical area from the lumbar injection. Conclusion: A blind epidural blood patch from the lumbar area is an acceptable procedure even if the area of leakage is unknown. A reasonable clinical procedure for the patients of SIH may minimize the rate of repeat puncture.