[Botulinum Toxin Treatment for Hemifacial Spasm:Based on the Practical Clinical Experience in the Neurology Outpatient Clinic].

Botulinum toxin(BTX)treatment is the first-line neurological treatment for hemifacial spasm(HFS). In my neurology clinic, Clinique Kita Neurologique(CKN), I have provided a cumulative total of approximately 400 BTX treatments for approximately 50 HFS patients for 23 years. Based on my own practical clinical experience, I have demonstrated the efficacy of BTX treatment. In compressive HFS, BTX treatment is indicated in patients who are not indicated or unwilling to undergo neurodecompression surgery. This is also indicated in the case of a long waiting period before surgery. In postparetic HFS, BTX treatment is indicated in patients with spasm and synkinesia. The amount of each BTX injection in postparetic HFS should be less than that in compressive HFS because of latent facial paresis. Although BTX injections can be easily administered in neurology outpatient clinics, it is important to perform the procedure safely and promptly.

[A Case of Hirayama Disease Presenting Horn Hand: Spinal Horn Hand].

A 28-year-old man with Hirayama disease presented with a peculiar hand posture called "horn hand" ("main en corne"). The patient noticed that he could not extend his 3rd and 4th fingers when extending the fingers of his right hand 1 year prior to presentation. On neurological examination, the strength of the finger extension is severely weak in the 1st, 3rd and 4th fingers, causing a drop finger posture, but it is only moderately weak in the 2nd and 5th fingers, enabling him to sustain the extension finger posture. The finger posture is like a bull's horns and is named "horn hand". Amyotrophy of the ulnar side of the right forearm, so-called "oblique amyotrophy", and amyotrophy of the right hand are observed. MRI examination reveals atrophy of the lower cervical spinal cord and compression of it in the neck flexion posture. Diagnosis of Hirayama disease (juvenile muscular atrophy of the distal upper extremity) is confirmed. Horn hand has been reported so far in some cases of lead neuropathy, chronic inflammatory demyelinating polyneuropathy, and distal myopathy; a "peripheral" horn hand is characterized by partial and selective lesion of the radial nerve or of the finger extensor muscles. Meanwhile, a "spinal" horn hand in this patient with Hirayama disease represents the partial and selective lesion of the spinal anterior horn neurons.

The scaffold-dependent function of RIPK1 in dendritic cells promotes injury-induced colitis.

Receptor interacting protein kinase 1 (RIPK1) is a cytosolic multidomain protein that controls cell life and death. While RIPK1 promotes cell death through its kinase activity, it also functions as a scaffold protein to promote cell survival by inhibiting FADD-caspase 8-dependent apoptosis and RIPK3-MLKL-dependent necroptosis. This pro-survival function is highlighted by excess cell death and perinatal lethality in Ripk1-/- mice. Recently, loss of function mutation of RIPK1 was found in patients with immunodeficiency and inflammatory bowel diseases. Hematopoietic stem cell transplantation restored not only immunodeficiency but also intestinal inflammatory pathology, indicating that RIPK1 in hematopoietic cells is critical to maintain intestinal immune homeostasis. Here, we generated dendritic cell (DC)-specific Ripk1-/- mice in a genetic background with loss of RIPK1 kinase activity and found that the mice developed spontaneous colonic inflammation characterized by increased neutrophil and Ly6C+ monocytes. In addition, these mice were highly resistant to injury-induced colitis. The increased colonic inflammation and the resistance to colitis were restored by dual inactivation of RIPK3 and FADD, but not by inhibition of RIPK3, MLKL, or ZBP1 alone. Altogether, these results reveal a scaffold activity-dependent role of RIPK1 in DC-mediated maintenance of colonic immune homeostasis.