Conus involvement and leptomeningeal enhancement in aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder: A case report.

There are a variety of clinical phenotypes and radiological features that continue to make a diagnosis of neuromyelitis optica spectrum disorder (NMOSD) challenging. We present an atypical case of an adult woman who presented with flaccid paralysis of all extremities with unusual neuroimaging features, including extensive enhancing lesions in the upper cervical cord and conus medullaris with associated leptomeningeal enhancement. She was ultimately found to have AQP4 antibody-positive NMOSD. We discuss the factors that complicated a timely diagnosis, including her atypical radiographic features and an initially negative cell-based assay for myelin oligodendrocyte glycoprotein (MOG) and aquaporin-4 (AQP4) antibodies. Despite the rarity of conus medullaris involvement or leptomeningeal enhancement in AQP4 antibody-positive NMOSD, it is important to maintain a high level of clinical suspicion to avoid diagnostic and therapeutic delays. Though cell-based assays have high sensitivities, testing should be repeated on negative values in these scenarios.

Neck-Tongue Syndrome.

Neck-tongue syndrome (NTS) is a headache disorder often initiated by rapid axial rotation of the neck resulting in unilateral neck and/or occipital pain and transient ipsilateral tongue sensory disturbance. In this review, we examine reported cases of NTS since its initial description in 1980 to highlight the significance of this condition in the differential diagnosis of headache in patients presenting with neck pain and altered tongue sensation. The anatomical basis of NTS centers on the C1-C2 facet joint, C2 ventral ramus, and inferior oblique muscle in the atlanto-axial space. NTS may be categorized as complicated (secondary to another disease process) or uncomplicated (hereditary, related to trauma, or idiopathic). Diagnosis is based on clinical suspicion after a thorough history and physical without a pathognomonic radiologic finding. It is typically treated conservatively with medications, local injections, immobilization with cervical collars, or physical therapy; rarely is surgical intervention pursued.

Systematic Review of Preventive and Acute Treatment of Menstrual Migraine.

OBJECTIVE: The aim of this systematic review is to identify the efficacy of different categories of treatments for menstrual migraines as found in randomized controlled trials or open label studies with similar efficacy endpoints. BACKGROUND: Menstrual migraine is very common and approximately 50% of women have increased risk of developing migraines related to the menstrual cycle. Attacks of menstrual migraine are usually more debilitating, of longer duration, more prone to recurrence, and less responsive to acute treatment than nonmenstrual migraine attacks. METHODS: Search for evidence was done in 4 databases that included PubMed, EMBASE, Science Direct, and Web of Science. Eighty-four articles were selected for full text review by 2 separate readers. Thirty-six of the 84 articles were selected for final inclusion. Articles included randomized controlled and open label trials that focused on efficacy of acute and preventative therapies for menstrual migraine. Secondary analyses where excluded because the initial study population was not women with menstrual migraine. RESULTS: After final screening, 11 articles were selected for acute and 25 for preventive treatment of menstrual migraine. These were further subdivided into treatment categories. For acute treatment: triptans, combination therapy, prostaglandin synthesis inhibitor, and ergot alkaloids. For preventive treatment: triptans, combined therapy, oral contraceptives, estrogen, nonsteroidal anti-inflammatory drug, phytoestrogen, gonadotropin-releasing hormone agonist, dopamine agonist, vitamin, mineral, and nonpharmacological therapy were selected. Overall, triptans had strong evidence for treatment in both acute and short term prevention of menstrual migraine. CONCLUSIONS: Based on this literature search, of all categories of treatment for menstrual migraine, triptans have the most extensive research with strong evidence for both acute and preventive treatment of menstrual migraine. Further randomized controlled trials should be performed for other therapies to strengthen their use in the care of menstrual migraine patients.

Menopause and menopausal symptoms after ovarian artery embolization: a comparison with uterine artery embolization controls.

PURPOSE: To determine the impact on menstrual status and menopausal symptoms of ovarian artery embolization (OAE) to supplement uterine embolization (UAE) for uterine leiomyomas. MATERIALS AND METHODS: A single-center case-control study was conducted in women who underwent UAE for leiomyomas. Between May 2004 and July 2009, 77 patients underwent unilateral or bilateral OAE during UAE procedures. Contemporaneous control subjects undergoing UAE alone were identified based on age and race. Questionnaires queried menstrual cycle regularity, onset of menopause, hormone use, and subsequent leiomyoma interventions, as well as the Menopause Rating Scale (MRS), a validated menopausal symptom questionnaire. Records were reviewed for baseline clinical and procedure data. Case and control subjects were compared for baseline characteristics and outcomes with the use of appropriate statistics, with the primary outcome the summary score on the MRS. RESULTS: Of 154 patients, 51 case subjects and 49 control subjects responded to the MRS (65%). Case subjects had greater tumor volumes (median, 129.3 cm(3) vs 69.3 cm(3) in control subjects; P = .0252) and longer fluoroscopy times (mean, 20.5 min vs 14 min in control subjects; P < .0001), with no other differences. There was a lower mean MRS score in the OAE group (total mean MRS score, 7.4 in case subjects and 8.9 in control subjects; P = .023), indicating fewer menopausal symptoms and no difference in menstrual regularity or frequency of onset of menopause. Of six patients who underwent bilateral OAE and responded, all reported continued menstrual cycles. CONCLUSIONS: Compared with standard UAE, the addition of OAE does not appear to precipitate the onset of menopause nor increase menopausal symptom severity.

Site-specific chemical modification of recombinant proteins produced in mammalian cells by using the genetically encoded aldehyde tag.

The properties of therapeutic proteins can be enhanced by chemical modification. Methods for site-specific protein conjugation are critical to such efforts. Here, we demonstrate that recombinant proteins expressed in mammalian cells can be site-specifically modified by using a genetically encoded aldehyde tag. We introduced the peptide sequence recognized by the endoplasmic reticulum (ER)-resident formylglycine generating enzyme (FGE), which can be as short as 6 residues, into heterologous proteins expressed in mammalian cells. Cotranslational modification of the proteins by FGE produced products bearing a unique aldehyde group. Proteins bearing this "aldehyde tag" were chemically modified by selective reaction with hydrazide- or aminooxy-functionalized reagents. We applied the technique to site-specific modification of monoclonal antibodies, the fastest growing class of biopharmaceuticals, as well as membrane-associated and cytosolic proteins expressed in mammalian cells.

Protein kinase C negatively regulates Akt activity and modifies UVC-induced apoptosis in mouse keratinocytes.

Skin keratinocytes are subject to frequent chemical and physical injury and have developed elaborate cell survival mechanisms to compensate. Among these, the Akt/protein kinase B (PKB) pathway protects keratinocytes from the toxic effects of ultraviolet light (UV). In contrast, the protein kinase C (PKC) family is involved in several keratinocyte death pathways. During an examination of potential interactions among these two pathways, we found that the insulin-like growth factor (IGF-1) activates both the PKC and the Akt signaling pathways in cultured primary mouse keratinocytes as indicated by increased phospho-PKC and phospho-Ser-473-Akt. IGF-1 also selectively induced translocation of PKCdelta and PKCepsilon from soluble to particulate fractions in mouse keratinocytes. Furthermore, the PKC-specific inhibitor, GF109203X, increased IGF-1-induced phospho-Ser-473-Akt and Akt kinase activity and enhanced IGF-1 protection from UVC-induced apoptosis. Selective activation of PKC by 12-O-tetradecanoylphorbol-13-acetate (TPA) reduced phospho-Ser-473-Akt, suggesting that activation of PKC inhibits Akt activity. TPA also attenuated IGF-1 and epidermal growth factor-induced phospho-Ser-473-Akt, reduced Akt kinase activity, and blocked IGF-1 protection from UVC-induced apoptosis. The inhibition of Akt activity by TPA was reduced by inhibitors of protein phosphatase 2A, and TPA stimulated the association of phosphatase 2A with Akt. Individual PKC isoforms were overexpressed in cultured keratinocytes by transduction with adenoviral vectors or inhibited with PKC-selective inhibitors. These studies indicated that PKCdelta and PKCepsilon were selectively potent at causing dephosphorylation of Akt and modifying cell survival, whereas PKCalpha enhanced phosphorylation of Akt on Ser-473. Our results suggested that activation of PKCdelta and PKCepsilon provide a negative regulation for Akt phosphorylation and kinase activity in mouse keratinocytes and serve as modulators of cell survival pathways in response to external stimuli.