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1.
Nat Commun ; 13(1): 3013, 2022 05 31.
Article in English | MEDLINE | ID: mdl-35641514

ABSTRACT

Pulmonary hypertension is a fatal rare disease that causes right heart failure by elevated pulmonary arterial resistance. There is an unmet medical need for the development of therapeutics focusing on the pulmonary vascular remodeling. Bioactive lipids produced by perivascular inflammatory cells might modulate the vascular remodeling. Here, we show that ω-3 fatty acid-derived epoxides (ω-3 epoxides) released from mast cells by PAF-AH2, an oxidized phospholipid-selective phospholipase A2, negatively regulate pulmonary hypertension. Genetic deletion of Pafah2 in mice accelerate vascular remodeling, resulting in exacerbation of hypoxic pulmonary hypertension. Treatment with ω-3 epoxides suppresses the lung fibroblast activation by inhibiting TGF-ß signaling. In vivo ω-3 epoxides supplementation attenuates the progression of pulmonary hypertension in several animal models. Furthermore, whole-exome sequencing for patients with pulmonary arterial hypertension identifies two candidate pathogenic variants of Pafah2. Our findings support that the PAF-AH2-ω-3 epoxide production axis could be a promising therapeutic target for pulmonary hypertension.


Subject(s)
Fatty Acids, Omega-3 , Hypertension, Pulmonary , Animals , Epoxy Compounds/pharmacology , Fatty Acids, Omega-3/pharmacology , Humans , Hypertension, Pulmonary/pathology , Mast Cells/pathology , Mice , Vascular Remodeling
2.
Neurology ; 92(4): e371-e377, 2019 01 22.
Article in English | MEDLINE | ID: mdl-30587520

ABSTRACT

OBJECTIVE: To report the safety and long-term efficacy of ventro-oral thalamotomy for 171 consecutive patients with task-specific focal hand dystonia. METHODS: Between October 2003 and February 2017, 171 consecutive patients with task-specific focal hand dystonia underwent unilateral ventro-oral thalamotomy. Etiologies included writer's cramps (n = 92), musician's dystonias (n = 58), and other occupational task-related dystonias (n = 21). The task-specific focal hand dystonia scale was used to evaluate patients' neurologic conditions (range 1-5, high score indicated a better condition). The scores before surgery; at 1 week, 3 months, and 12 months postoperatively; and the last available follow-up period were determined. Postoperative complications and postoperative recurrence were also evaluated. RESULTS: The scores before surgery; at 1 week (1.72 ± 0.57, 4.33 ± 0.85 [p < 0.001]), 3 months (4.30 ± 1.06 [p < 0.001]), and 12 months (4.30 ± 1.13 [p < 0.001]); and the last available follow-up (4.39 ± 1.07 [p < 0.001]) postoperatively improved. The mean clinical follow-up period was 25.4 ± 32.1 months (range: 3-165). Permanent adverse events developed in 6 patients (3.5%). Eighteen patients developed recurrent dystonic symptoms postoperatively. Of these 18 patients, 9 underwent ventro-oral thalamotomy again, of which 7 achieved improvement. CONCLUSION: Ventro-oral thalamotomy is a feasible and reasonable treatment for patients with refractory task-specific focal hand dystonias. Prospective, randomized, and blinded studies are warranted to clarify more accurate assessment of the safety and efficacy of ventro-oral thalamotomy for task-specific focal hand dystonia. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with task-specific focal hand dystonia, ventro-oral thalamotomy improves dystonia.


Subject(s)
Dystonic Disorders/surgery , Neurosurgical Procedures/methods , Thalamus/surgery , Treatment Outcome , Adolescent , Adult , Aged , Female , Humans , Longitudinal Studies , Male , Middle Aged , Retrospective Studies , Young Adult
3.
Stereotact Funct Neurosurg ; 94(4): 201-206, 2016.
Article in English | MEDLINE | ID: mdl-27434121

ABSTRACT

BACKGROUND: Hairdresser's dystonia is a rarely reported form of focal hand dystonia, and the clinical course and treatment remains poorly understood. OBJECTIVES: The aim of this report was to clarify the impact of thalamotomy on hairdresser's dystonia. METHODS: Four consecutive patients with hairdresser's task-specific dystonia evaluated at Tokyo Women's Medical University Hospital between 2008 and 2013 were treated with stereotactic thalamotomy, and were recruited for this case series. RESULTS: The mean age at the onset of symptoms was 37.25 ± 10.64 years, the median duration of symptoms was 4.25 ± 1.3 years, and the mean follow-up period was 17 ± 12.37 months. Two of the 4 patients returned to work with significant improvement following the stereotactic thalamotomy and the beneficial effects persisted for the duration of their clinical follow-up. The other 2 patients experienced transient improvements for up to 3 months. Surgical complications included only dysarthria in 2 patients, and did not interfere with their daily activities. No patients experienced a deterioration of dystonic symptoms after thalamotomy. CONCLUSION: Although the benefits of thalamotomy remain vulnerable to incorrect or insufficient coagulation, stereotactic thalamotomy may be a feasible and effective procedure for patients with hairdresser's dystonia.


Subject(s)
Dystonic Disorders/surgery , Thalamus/surgery , Adult , Catheter Ablation , Humans , Male , Middle Aged , Neurosurgical Procedures , Stereotaxic Techniques
4.
Stereotact Funct Neurosurg ; 94(3): 129-33, 2016.
Article in English | MEDLINE | ID: mdl-27172923

ABSTRACT

BACKGROUND/AIMS: Although many reports have confirmed the effects of stereotactic thalamotomy for writer's cramp, pallidotomy for writer's cramp is yet to be investigated. METHODS: After a 22-year-old woman with writer's cramp had undergone stereotactic thalamotomy twice, symptomatic relief was only temporary. Because her dystonic symptoms spread around the proximal part of the upper limb, she underwent unilateral pallidotomy 21 months after the second thalamotomy. RESULTS: Unilateral pallidotomy improved her dystonic symptoms without any adverse effects immediately after the surgery. During a follow-up observation of 1 year, no recurrent writer's cramp was observed. CONCLUSION: For writer's cramp, when symptoms cannot be improved by thalamotomy, pallidotomy may achieve an effective outcome.


Subject(s)
Dystonic Disorders/surgery , Pallidotomy/methods , Thalamus/surgery , Female , Humans , Recurrence , Reoperation , Stereotaxic Techniques , Young Adult
5.
World Neurosurg ; 92: 585.e21-585.e25, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27188636

ABSTRACT

BACKGROUND: Focal hand dystonia in musicians, also known as musician's dystonia, is a task-specific movement disorder characterized by unwanted involuntary muscle contractions occurring only when playing a musical instrument. CASE DESCRIPTION: Case 1 was a 50-year-old female professional pianist who underwent staged bilateral ventro-oral (Vo) thalamotomy, with an interval between the first and second surgery of 4 years. The first surgery (right Vo thalamotomy) led to significant improvements in dystonic symptoms without any complications. Pre- and postoperative Tubiana's musician's dystonia scale (TMDS) scores were 2 and 5, respectively. The second surgery (left Vo thalamotomy) also led to significant improvements in dystonic symptoms, with dysarthria and verbal recall disturbance resolving within 3 months. Pre- and postoperative TMDS scores were 2 and 5, respectively. The patient was subsequently able to return to live-stage performances. Case 2 was a 48-year-old male clarinet repair technician who underwent staged bilateral Vo thalamotomy, with an interval between the first and second surgery of 13 months. The first surgery (right Vo thalamotomy) led to dramatic improvements in symptoms without any complications. Pre- and postoperative TMDS scores were 2 and 5, respectively. The second surgery (left Vo thalamotomy) also led to significant improvements in symptoms with transient hypophonia. Pre- and postoperative TMDS scores were 2 and 5, respectively. The patient was subsequently able to return to work without difficulty. CONCLUSIONS: The findings in these 2 cases indicate the utility of bilateral stereotactic Vo thalamotomy in the treatment of medically intractable musician's dystonia affecting both hands.


Subject(s)
Dystonic Disorders/surgery , Music , Stereotaxic Techniques , Thalamus/physiology , Dystonic Disorders/diagnostic imaging , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Thalamus/surgery , Treatment Outcome
6.
Ann Neurol ; 74(5): 648-54, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23463596

ABSTRACT

OBJECTIVE: Musician's dystonia is a task-specific movement disorder that causes twisting or repetitive abnormal finger postures and movements, which tend to occur only while playing musical instruments. Such a movement disorder will probably lead to termination of the careers of affected professional musicians. Most of the currently available treatments have yet to provide consistent and satisfactory results. We present the long-term follow-up results of ventro-oral thalamotomy for 15 patients with musician's dystonia. METHODS: Between October 2003 and September 2010, 15 patients with medically intractable task-specific focal hand dystonia that occurred only while playing musical instruments underwent ventro-oral thalamotomy. We used Tubiana's musician's dystonia scale to evaluate the patients' pre- and postoperative neurological conditions. RESULTS: All patients except 1 (93%) experienced dramatic improvement of dystonic symptoms immediately after ventro-oral thalamotomy. The mean follow-up period was 30.8 months (range=4-108 months). None of the patients experienced recurrence or deterioration of symptoms during the follow-up periods. INTERPRETATION: Ventro-oral thalamotomy remarkably improved musician's dystonia, and the effect persisted for a long duration.


Subject(s)
Dystonic Disorders/surgery , Thalamus/surgery , Adult , Female , Humans , Male , Middle Aged , Stereotaxic Techniques , Treatment Outcome
7.
Brain Nerve ; 64(11): 1307-13, 2012 Nov.
Article in Japanese | MEDLINE | ID: mdl-23131742

ABSTRACT

Different surgical procedures are available for the treatment of many neuropathic pain syndromes. These surgical procedures can be divided into 2 main sections: non-destructive and destructive procedures. In recent years, the non-destructive neurostimulation method has undergone rapid development. Neurostimulation can be applied to a large part of the nervous system including the brain, spinal cord, and peripheral nerves. Spinal cord stimulation has become a dominant pain relief modality because of its minimal invasiveness and the development of a multi-contact stimulating electrode system powered by a multi-programmable and rechargeable stimulator. Currently, destructive surgical procedures have a limited range of indications for pain control. However, the advantages of destructive procedures over non-destructive ones include continuous pain reduction without implantation of a stimulation system. Each of the surgical procedures has great potential for providing patients with significant relief from neuropathic pain.


Subject(s)
Electric Stimulation Therapy/methods , Neuralgia/therapy , Peripheral Nerves/surgery , Deep Brain Stimulation/methods , Humans , Spinal Cord Stimulation/instrumentation , Spinal Cord Stimulation/methods , Treatment Outcome
8.
Masui ; 58(9): 1158-61, 2009 Sep.
Article in Japanese | MEDLINE | ID: mdl-19764441

ABSTRACT

The authors describe an experience of spinal cord stimulation (SCS) in a 30-year-old woman who developed complex regional pain syndrome type-I (CRPS-I) with spread phenomenon. She had received lumbar SCS under a diagnosis of CRPS-I in her left leg for 8 years. She had refractory pain in her right arm for the recent two years. There was no new lesion explaining her refractory pain on physical or radiological examination. Thus, the pain in her right upper arm was considered as spread phenomenon of CRPS-I. Test stimulation with cervical epidural spinal electrode showed good results and the pulse generator was implanted. It is suggested that the symptom of CRPS-I involving spread phenomenon was possibly due to a cortical reorganization. But a certain effect of SCS may be contributing to the favorable results of test stimulation for the treatment of CRPS-I with spread phenomenon in this case.


Subject(s)
Electric Stimulation Therapy/methods , Reflex Sympathetic Dystrophy/therapy , Spinal Cord/physiology , Adult , Disease Progression , Electrodes, Implanted , Female , Humans , Treatment Outcome
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