Christina Fan’s scientific contributions

In article number 1902583, Roland Beisteiner and co‐workers describe a brain activation technique for treatment of Alzheimer's disease. Transcranial pulse stimulation (TPS) applies ultrashort ultrasound pulses to activate neuronal resources. A therapeutic breakthrough is secure clinical targeting and access to deep brain areas. After 2 weeks of treatment, memory performance improves for up to 3 months.

Context/objective: Focused extracorporeal shock waves upregulate vascular endothelial growth factor, endothelial nerve growth factor, endothelial nitric oxide production, and the production, differentiation, and migration of stem cells. We attempted to test whether low-energy focused extracorporeal shock wave therapy (ESWT) can improve the symptoms of paraplegia. Design: Case report. Setting: Common documentation of data during rehabilitation courses. Participants: Five adults who suffered from different degrees of paraplegia secondary to trauma. Interventions: ESWT was applied to spinal cord lesions several times a week. All patients received two to three weeks of complex therapy consisting of daily manual medicine, massages to stimulate proprioception, neurophysiology-based physiotherapy, occupational therapy, and, whenever indicated, medical mechanical therapy with a swing, motor-driven treadmills used in a supine or upright position, and a vibration system. Outcome measures: The courses of treatment were documented using surface electromyography (EMG), manual muscle test (MMT), and functional reach (FR) test. Results: In all patients, previously poor or not-activated muscles showed increased EMG activity. FR and MMT improved by an average of 9.8 cm and 2.1 grades, respectively. In some patients, superficial and deep sensibility increased below the lesion. No undesirable side effects were reported. Conclusion: ESWT is a safe, non-invasive method that improves paraplegic symptoms in the areas innervated by the nerve roots below the spinal lesion.

Statement of problem: Can low-energy focused extracorporeal shock wave therapy (ESWT) improve symptoms of a paraparesis? Patients and Methods: 2 girls, 11, 12 years of age, suffering from paraparesis caused by myelomeningocele, received ESWT ("Duolith" shock wave generator, Storz Medical) to the region of the spinal cord lesion several times a week. This treatment was part of a complex therapy regime. The courses of treatment were documented using surface EMG, manual muscle test (MMT), and functional reach test (FR). Results: Previously non-innervated muscles that were rated subsequently showed increasing EMG activity and an average improvement in strength of about 3°-4 ° in MMT. The patients improved their FR when seated by 5 cm and 14 cm respectively. The degree of the American Spinal Injury Association (ASIA) classification evolved from ASIA A to C and D. Superficial and deep sensibility increased below the lesion level. There were no undesirable side effects. Discussion: Suitable doses of ESWT stimulate muscles and nerves directly and may lead furthermore to the release of neurotrophic substances. Conclusions: ESWT enhance muscular function and superficial sensibility in the lower adjacent region of the spinal cord lesion in children with myelomeningocele. The neurophysiological effects need to be verified on larger numbers of patients.

Ultrasound‐based brain stimulation techniques may become a powerful new technique to modulate the human brain in a focal and targeted manner. However, for clinical brain stimulation no certified systems exist and the current techniques have to be further developed. Here, a clinical sonication technique is introduced, based on single ultrashort ultrasound pulses (transcranial pulse stimulation, TPS) which markedly differs from existing focused ultrasound techniques. In addition, a first clinical study using ultrasound brain stimulation and first observations of long term effects are presented. Comprehensive feasibility, safety, and efficacy data are provided. They consist of simulation data, laboratory measurements with rat and human skulls and brains, in vivo modulations of somatosensory evoked potentials (SEP) in healthy subjects (sham controlled) and clinical pilot data in 35 patients with Alzheimer's disease acquired in a multicenter setting (including neuropsychological scores and functional magnetic resonance imaging (fMRI)). Preclinical results show large safety margins and dose dependent neuromodulation. Patient investigations reveal high treatment tolerability and no major side effects. Neuropsychological scores improve significantly after TPS treatment and improvement lasts up to three months and correlates with an upregulation of the memory network (fMRI data). The results encourage broad neuroscientific application and translation of the method to clinical therapy and randomized sham‐controlled clinical studies. A new clinical brain stimulation technique is introduced, based on single ultrashort ultrasound pulses (transcranial pulse stimulation, TPS). Comprehensive feasibility, safety, and efficacy data for this new therapy are provided. Two weeks TPS treatment of 35 Alzheimer's patients reveals high treatment tolerability, no major side effects, and improved memory performance lasting up to three months.