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.

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.

OBJECTIVE: Can stimulation of nerve growth factors by focused transcranial extracorporeal shock wave therapy (TESWT) be made effective for persons within unresponsive wakefulness syndrome (apallic syndrome)? DESIGN: Between eight and 18 years after the brain lesion, five patients with unresponsive wakefulness syndrome of differing severity received TESWT with the device Duolith (Storz Medical) during four-week physicomedical complex therapies. In the previous years they had been treated with the same complex therapies without TESWT. The vigilance did not change. RESULTS: After two-four years and an average of 5.2 treatment series, the patients' abilities improved by 135.9% on the German Coma Remission Scale (KRS) and by 43.6% on the Glasgow Coma Scale. In the motor area of the KRS, the patients improved by 64.3%. Three PEG feeding tubes could be removed, nonverbal communication initiated four times. CONCLUSION: In this longitudinal observation study, focused TESWT stimulated vigilance in patients with unresponsive wakefulness syndrome. The precise neurophysiological effects remain to be verified by a study of the clinical results.

BACKGROUND: Incidental observations led to the question whether ESWT could alleviate the still difficult-to-improve symptoms of DSPNP. METHODS: In a pilot study, out of an original 24 patients with DSPNP, 10 patients with diabetes mellitus were excluded because of their inhomogeneous performances. Of the 14 patients remaining, 6 received one sham treatment at the beginning. All 14 patients were then treated with ESWT to the soles of the feet using the Duolith ® shock wave generator (Storz Medical) 3 times weekly for 2 weeks. The assessments were carried out before and after the sham treatment, the first ESWT (question: before and after the first ESWT or only after?) and after 2, 4 and 8 weeks. RESULTS:The placebo treatment did not influence pain or paraesthesia. After the 2 weeks of ESWT, intensity decreased from 100% to 23.6%, rising again after 8 weeks to 45.7% of the original state (p < 0.01). The placebo treatment did however have a great effect on walking abilities. The results of ESWT did not become significant until the 8th week.Step length improved by 14.6% (p < 0.001), walking speed by 24.8% (p < 0.001) and time of dual support during the stance phase of the gait declined by 12.2% (p < 0.009). CONCLUSIONS: Despite the small number of cases, it appears that ESWT can alleviate some of the symptoms of DSPNP.

ESW is suitable for use as an additional instrument for physiotherapeutic treatment of infantile cerebral palsy. The effective action of ESW on disturbed peripheral muscles has been discussed in terms of positive pressure and tensile wave forces and/or forces acting by cavitation. The results obtained in this pilot investigation showed particular a decrease in muscle stiffness. A controlled investigation with gait analysis and psychological control is to be undertaken.