Multimodal treatment, including extracorporeal shock wave therapy, for refractory chronic tension-type headache: a case report

Abstract Background Few reports have described multidisciplinary treatment, including extracorporeal shock wave therapy, for patients with refractory chronic tension-type headache. In this study, we conducted multidisciplinary treatment for a patient with chronic tension-type headache who suffered from chronic headache refractory to treatment. Case presentation The patient was a 45-year-old Japanese male suffering from 20 years of headache. As his headache had worsened recently, he visited a local clinic. With the diagnosis of suspected tension-type headache, its treatment was unsuccessful and he was referred to our hospital. The neurology department confirmed the tension-type headache and prescribed another medication, but he showed no improvement. Then, the patient was referred to the rehabilitation medicine department for consultation. At the initial visit, we identified multiple myofascial trigger points in his bilateral posterior neck and upper back regions. At the initial visit, he was prescribed 10 mL of 1% lidocaine injected into the muscles in these areas. In addition, he received 2000 extracorporeal shock wave therapy into bilateral trapezius muscles, and was instructed to take oral Kakkonto extract granules, benfotiamine, pyridoxine hydrochloride, and cyanocobalamin. Cervical muscle and shoulder girdle stretches and exercises were also recommended. At follow-up treatment visits, we used extracorporeal shock wave therapy to bilateral trapezius muscles, which led to immediate pain relief. After 11 weeks, he was not taking any medication and his headache was subjectively improved and his medical treatment ended. Conclusion A patient with chronic tension-type headache refractory to regular treatment was successfully treated with a multimodal approach including extracorporeal shock wave therapy in addition to standard treatment. For patients with tension-type headache accompanied by myofascial trigger points, it may be recommended to promptly consider aggressive multimodal treatment that includes extracorporeal shock wave therapy

UTX and UTY Demonstrate Histone Demethylase-Independent Function in Mouse Embryonic Development

<div><p>UTX (KDM6A) and UTY are homologous X and Y chromosome members of the Histone H3 Lysine 27 (H3K27) demethylase gene family. UTX can demethylate H3K27; however, <em>in vitro</em> assays suggest that human UTY has lost enzymatic activity due to sequence divergence. We produced mouse mutations in both <em>Utx</em> and <em>Uty</em>. Homozygous <em>Utx</em> mutant female embryos are mid-gestational lethal with defects in neural tube, yolk sac, and cardiac development. We demonstrate that mouse UTY is devoid of <em>in vivo</em> demethylase activity, so hemizygous X<em>^Utx−</em> Y<em>⁺</em> mutant male embryos should phenocopy homozygous X<em>^Utx−</em> X<em>^Utx−</em> females. However, X<em>^Utx−</em> Y<em>⁺</em> mutant male embryos develop to term; although runted, approximately 25% survive postnatally reaching adulthood. Hemizygous X<em>⁺</em> Y<em>^Uty−</em> mutant males are viable. In contrast, compound hemizygous X<em>^Utx−</em> Y<em>^Uty−</em> males phenocopy homozygous X<em>^Utx−</em> X<em>^Utx−</em> females. Therefore, despite divergence of UTX and UTY in catalyzing H3K27 demethylation, they maintain functional redundancy during embryonic development. Our data suggest that UTX and UTY are able to regulate gene activity through demethylase independent mechanisms. We conclude that UTX H3K27 demethylation is non-essential for embryonic viability.</p> </div

Hemizygous male <i>Utx</i> mutant mice are runted.

<p>(A) Hemizygous male <i>Utx</i> mutant mice are runted in size. Wild type male X<i>^Utx</i>⁺ Y⁺ mice are displayed next to hemizygous X<i>^UtxGT1</i> Y⁺ mice. (B) The hemizygous mice exhibit a smaller size throughout adulthood.</p

<i>Utx</i> mutant alleles.

<p>(A) Schematics of mouse mutations in <i>Utx</i>. Included are annotations and locations of where the protein would be mutated. Two <i>Utx</i> mutant alleles included a gene trap in intron 3 (X<i>^UtxGT1</i>) and a gene trap/floxed exon 3 (X<i>^UtxGT2fl</i>). A UTX protein annotation is illustrated at the top to indicate to positions of <i>Utx</i> alleles. A germline Cre recombinase deleted exon 3 in the X<i>^UtxGT2fl</i> background to create X<i>^UtxGT2Δ</i>. Additionally, the gene trap of X<i>^UtxGT2fl</i> was excised with Flp recombinase to create a standard floxed exon 3 (X<i>^Utxfl</i>) and Cre recombination created X<i>^UtxΔ</i>. (B) Western blotting of E18.5 liver demonstrates a complete loss of UTX in X<i>^UtxGT1</i> Y<i>^Uty+</i> lysates. RbBP5 was used as a loading control. (C) Western blotting of E10.5 whole embryo demonstrates a complete loss of UTX in X<i>^UtxΔ</i> Y<i>^Uty+</i> and X<i>^UtxΔ</i> X<i>^UtxΔ</i> lysates. RbBP5 was used as a loading control. (D) Western blotting of E12.5 primary MEFs demonstrates a reduction of UTX in X<i>^UtxGT2fl</i> Y<i>^Uty+</i> and X<i>^UtxGT2fl</i> X<i>^UtxGT2fl</i> lysates. RbBP5 was used as a loading control.</p