Switching From Pregabalin to Mirogabalin in Patients with Peripheral Neuropathic Pain: A Multi-Center, Prospective, Single-Arm, Open-Label Study (MIROP Study).

INTRODUCTION: Mirogabalin, which is a selective ligand of the α2δ subunit of voltage-gated Ca2+ channels, was recently approved in Japan for peripheral neuropathic pain. The α2δ ligands, including mirogabalin and pregabalin, are associated with significant risk of adverse events (AEs) such as somnolence or dizziness, leading to poor compliance and subsequent inefficacy. Safety and efficacy data for switching patients from pregabalin to mirogabalin are scarce. METHODS: This prospective, single-arm, open-label study involving ten participating centers in Japan recruited patients aged ≥ 20 years with peripheral neuropathic pain [visual analog scale (VAS) score ≥ 40 mm]. Where necessary, patients underwent a 1-week tapering period to reduce their pregabalin dose, after which pregabalin was stopped and mirogabalin dose was increased using a step-wise dose titration. Patients underwent dose increases after the first and second weeks if there were no tolerability issues, followed by the effective doses until the end of the study (4 weeks). The primary endpoint was the incidence of somnolence, dizziness, and peripheral edema; secondary endpoints included changes in VAS score. AEs were monitored for safety. RESULTS: Of 157 patients who provided informed consent, 152 patients were enrolled; 136 (89.5%) patients completed the study. The overall incidences of somnolence, dizziness, and peripheral edema were 41.4, 15.8, and 2.6%, respectively. Most patients (> 70%) experienced mild AEs, and one patient experienced a severe AE (dizziness). Most patients (> 70%) were able to achieve dose titration to an effective dose. Overall mean VAS score significantly decreased (Δ15.7 mm, p < 0.0001) by the end of the study. CONCLUSIONS: Mirogabalin switching from pregabalin is well tolerated and effective in pain management for peripheral neuropathic pain using a step-wise titration. TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCTs031190113).

[The Rehabilitation in Pain Clinic].

Rehabilitation is becoming an important field of care at pain clinics designed to alleviate pain. Exercise and physical therapies are widely used in rehabilitation, and exercise therapy in particular is considered a treatment that should be actively incorporated. Intervention must continue to be provided after ascertaining whether exercise therapy is within the scope of pain clinicians themselves, or whether it should be offered in collaboration with physical therapists. This can be achieved by deepening knowledge of exercise therapy and investigating how it should be offered depending on the disease. Focus should be placed on abnormal posture and exercise, as well as secondary pain. Visualizing movement and building up associated sensorimotor experiences are also considered important. To achieve this, cooperation between physiatrists and physical therapists, they must deepen and exchange understanding and knowledge with each other.

Perioperative management for a patient with hypermagnesemia-induced shock with perforative peritonitis.

We present a case of hypermagnesemia accompanied by perforative peritonitis. A 79-year-old woman took magnesium citrate as part of the pretreatment on the day before a scheduled colonoscopy. She developed nausea and muscle weakness, and she was complaining of left abdominal pain. Consciousness gradually worsened and she developed shock. Intestinal obstruction was recognized on abdominal X-ray and computed tomography (CT), and peritonitis was suspected. An exploratory laparotomy was scheduled for diagnosis and treatment. In the operating room, arterial blood gas analysis showed metabolic acidosis and hypermagnesemia (Mg: 2.75 mmol/l, normal range: 0.1-1.5 mmol/l). On laparotomy, adhesion around the sigmoid colon and turbid ascites were recognized. But we could not detect the apparent region of perforation. Based on these findings and the presence of hypermagnesemia, we diagnosed that the shock was caused by peritonitis due to intestinal micro-perforation, and by hypermagnesemia due to absorption of laxative. We started to treat for metabolic acidosis, and to manage the hypermagnesemia by calcium hydrochloride administration and by continuous hemodiafiltration after the operation. On day 4 of the illness, the plasma Mg level was normalized. She was extubated on day 12, and discharged on day 84. This case with complicated clinical symptoms reaffirms the difficulty and importance of making a diagnosis quickly by collecting various data.

Acute lymphocytic leukemia recurring in the spinal epidural space.

A 27-year-old man presented with a very rare spinal epidural mass associated with recurrence of acute lymphocytic leukemia (ALL) manifesting as acute progressive neurological deficits. The patient presented with shoulder pain and ambulatory difficulties 3 years after remission of ALL treated by bone marrow transplantation. Magnetic resonance imaging revealed an epidural mass extending from C-7 to T-3, which compressed the cord and extended to the intervertebral foramen along the roots. After decompression surgery, the symptoms dramatically improved. Histological examination showed clusters of immature lymphocytes consistent with recurrence of leukemia, so chemotherapy and radiation therapy were carried out. At 1 year after the operation, no local mass expansion or systemic progression of leukemia had occurred. Leukemic mass must be considered in the differential diagnosis of spinal epidural mass, even in patients with ALL.

Hemangioblastoma of the optic nerve--case report.

A 64-year-old man presented with a rare sporadic hemangioblastoma arising in the left optic nerve manifesting as left visual disturbance gradually progressive over 5 years. Magnetic resonance imaging revealed a well-enhanced mass in the left optic nerve. Partial resection of the tumor was performed via the frontoorbital approach. The histological diagnosis was optic nerve hemangioblastoma. Hemangioblastoma must be considered in the differential diagnosis of optic nerve tumors even in the absence of other lesions associated with von Hippel-Lindau disease.

[Intracranial chondroma arising from the skull base: two case reports featuring the image findings for differential diagnosis].

We reported two cases of intracranial skull base chondroma and discussed the differential diagnosis and the treatment strategies. The first case was a 39-year-old male who presented with left exophtalmos, visual loss and oculomotor disturbance. MRI showed a huge tumor occupying the bilateral cavernous sinus. Partial removal of the tumor was performed through the left orbitozygomatic subtemporal approach. The second case was a 54-year-old male who presented with left hemiparesis. MRI showed a brain stem infarction with a huge tumor located at the right middle fossa. Partial removal was performed through the right orbitozygomatic subtemporal approach. In these two cases, the histopathological diagnosis of the tumors was benign chondroma and the size of residual tumors have not changed for one year without any additional therapy. Although preoperative definite diagnosis for skull base chondromas is difficult, strategies for diagnosis and treatment without any complication are essential. In our cases, chondromas showed low uptake in PET images, which might be useful for differentiation between chondromas and chordomas. The current popular surgical approach for parasellar tumors is transcranial such as the orbitozygomatic subtemporal approach. In surgical removal of skull base chondromas, it is advisable to try to confirm the diagnosis preoperatively with characteristic image findings and to consider the best approach in each case to decompress the involved nerves without any complications.

[Iatrogenic peripheral nerve injury; mechanism and therapy].

The pain remaining after a needle stick is categorized as neuropathic pain. CRPS (Complex Regional Pain Syndrome) is a typical disease in this category. Neuropathic pain is extremely intractable when it becomes chronic pain, inducing psychological and physical pain in patients over a long period of time. Neuropathic pain is a complex system caused by various factors, and its mechanism remains unclear. For prevention, medical practioners should carefully select centesis, and apply necessary measures corresponding to the situation. There is no established treatment for neuropathic pain. We usually treat the disease with nerve block and drug therapy. Nerve block is useful for pain relief. We typically use a sympathetic nerve block (SGB; stellate ganglion block, IRSB; intravenous regional sympathetic block et. al.) as the initial treatment. In the stage of chronic pain, it is very important to improve patients' ADL (activity of daily living) and QOL (quality of life). If neuropathic pain is suspected, it is crucial to treat at an early stage. Therefore, it should be emphasized that when pain persists after a needle stick, the patient should immediately consult a pain clinician or an orthopedist.

[Complex regional pain syndrome type I induced by phenobarbital].

Complex regional pain syndrome type I (CRPS-I) requires the presence of regional pain and sensory changes associated with findings such as abnormal skin color, temperature change, sudomotor activity, or edema, following a noxious event. Complex regional pain syndrome type I induced by phenobarbital (PB) is not well known, although several reports have strengthened the association between PB and CRPS-I. I reviewed the charts of 99 patients treated with PB to assess the incidence, clinical characteristics, investigations, dosage and plasma concentration of PB, and risk factors in the development of CRPS-I. Six patients developed CRPS-I. Pain was severe and allodynia, swelling, discoloration, sweating were present in all patients. This syndrome manifested bilaterally in some patients. Affected patients included 5 men and 1 woman between the ages of 52 and 78 (average 64.2 years). A radiograph showed demineralization in one patient. Thermography showed temperature differences between affected and unaffected limbs, although in a few patients the differences were little because of bilateral affected limbs. 99Technetium methlyene diphosphonate bone scan showed increased periarticular changes in most of the patients. The patients developed CRPS-I at 9.7 weeks (average) after PB was begun. The average time was 7.5 months between CPRS-I and PB reduction. Neither sympathetic ganglion blockade nor physical therapy was effective. Treatment of CRPS-I consists of PB reduction and prednisone and/or Neurotropin. In all patients clinical symptoms and signs such as pain and edema, and range of motion of their shoulders were improved after PB discontinuation. One patient was followed longitudinally, documenting improvement following discontinuation, reexacerbation with PB rechallenge, and remission once more when PB were discontinued. The higher incidence should depend on the coexistence of separate risk factors such as age and PB dosage. Recognition of CRPS-I induced PB, early diagnosis, and withdrawal of PB are important for symptomatic relief and improvement of QOL.

[A case of intractable lower limb pain treated successfully by spinal cord stimulation with an electrode inserted retrogradely].

We experienced a case of intractable lower limb pain successfuly treated by spinal cord stimulation with an electrode inserted retrogradely. The patient is a 32 year-old-man suffering from intractable lower limb pain on the area innervated by the sciatic nerve from unidentified cause for about 4 years. We tried various treatments such as epidural block, S 1 nerve-root block including thermocoagulation technique, opiate. Nevertheless, his pain became worse further. Therefore, 6 years after the onset of the symptom, we tried to stimulate electrically the nerve with an electrode inserted retrogradely. This method of spinal cord stimulation produced enough pain reduction. The method of retrograde insertion of an electrode for spinal cord stimulation seems to be a good way to treat intractable pain of the area innervated by a single spinal nerve.

Intraoperative power Doppler ultrasonography with a contrast-enhancing agent for intracranial tumors.

OBJECT: The goal of this study was to evaluate intraoperative power Doppler ultrasonography when used with a contrast-enhancing agent for operations on intracranial tumors. METHODS: Forty intracranial tumors were examined using power Doppler ultrasonography with a galactose microparticle-based ultrasonographic contrast-enhancing agent during operations on the brain. The tumors included 37 intracranial neoplasms (14 gliomas, six meningiomas, three hemangioblastomas, two malignant lymphomas, three other primary neoplasms, nine metastatic tumors, and three nonneoplastic lesions). All patients also underwent computerized tomography and magnetic resonance imaging, and all but three of the patients underwent digital subtraction (DS) angiography. Before injection of the ultrasonographic contrast agent, intra- and peritumoral power Doppler flow signals were detected in 32 of the intracranial tumors. After the injection, the signals were enhanced in blood vessels around the tumors and in the tumor parenchyma in 36 tumors. The duration of contrast enhancement continued for 70 to 365 seconds (mean 251.8 +/- 69 seconds) after the injection. Among the tumors, hemangioblastomas displayed particularly strong contrast enhancement. In these intracranial tumors, the echo signals obtained using contrast-enhanced power Doppler ultrasonography correlated with DS angiographic staining. Power Doppler ultrasonograms with the appropriate contrast agent provided better data on the precise real-time position of the tumors and their relationship to adjacent vessels than ultrasonograms obtained before the injection of the contrast agent. CONCLUSIONS: Intraoperative power Doppler ultrasonography performed using a contrast-enhancing agent can facilitate intraoperative real-time navigation and assessment of the intratumoral vasculature and peritumoral vessels, particularly for tumors having abundant vessels such as hemangioblastomas.

[Rosai-Dorfman disease accompanying hypertrophic cranial pachymeningitis with an early symptom of right peripheral facial palsy].

We experienced a rare case of sinus histiocytosis with massive lymphoadenopathy (Rosai-Dorfman disease) accompanying hypertrophic cranial pachymeningitis. The patient is a 64-year-old woman with an early symptom of rt. peripheral facial palsy. She had a 4-month history of headache with a 5-week history of numbness in the rt. supraorbital nerve area, and lost her weight by 10 kg in 2 months. She developed rt. trochlea nerve palsy and numbness in the lt. mandibular nerve area. Laboratory findings showed that ALP, LDH and CRP were higher than normal. Of CT, MRI and MRA, the images of her head were normal. However, the Gd-enhanced MRI only showed a diffuse pachymeningeal enhancement. After about 3 months from the onset of rt. peripheral facial palsy, she died of DIC of unknown etiology. As a result of examinations in anatomical pathology, she was diagnosed as having sinus histiocytosis with massive lymphoadenopathy (Rosai-Dorfman disease). There were a large number of histiocytes on the pachymeninx. These findings suggest that hypertrophic cranial pachymeningitis caused multiple cranial neuropathy. We emphasize that use of Gd-enhanced MRI in the early stage is important for diagnosis.