Magnetic resonance-guided focused ultrasound (MRgFUS) is an emerging new technology with considerable potential to treat various neurological diseases. With refinement of ultrasound transducer technology and integration with magnetic resonance imaging guidance, transcranial sonication of precise cerebral targets has become a therapeutic option. Intensity is a key determinant of ultrasound effects. High-intensity focused ultrasound can produce targeted lesions via thermal ablation of tissue. MRgFUS-mediated stereotactic ablation is non-invasive, incision-free, and confers immediate therapeutic effects. Since the US Food and Drug Administration approval of MRgFUS in 2016 for unilateral thalamotomy in medication-refractory essential tremor, studies on novel indications such as Parkinson's disease, psychiatric disease, and brain tumors are underway. MRgFUS is also used in the context of blood-brain barrier (BBB) opening at low intensities, in combination with intravenously-administered microbubbles. Preclinical studies show that MRgFUS-mediated BBB opening safely enhances the delivery of targeted chemotherapeutic agents to the brain and improves tumor control as well as survival. In addition, BBB opening has been shown to activate the innate immune system in animal models of Alzheimer’s disease. Amyloid plaque clearance and promotion of neurogenesis in these studies suggest that MRgFUS-mediated BBB opening may be a new paradigm for neurodegenerative disease treatment in the future. Here, we review the current status of preclinical and clinical trials of MRgFUS-mediated thermal ablation and BBB opening, described their mechanisms of action, and discuss future prospects.
Alzheimer Disease ; Blood-Brain Barrier ; Brain ; Brain Neoplasms ; Essential Tremor ; High-Intensity Focused Ultrasound Ablation ; Immune System ; Magnetic Resonance Imaging ; Microbubbles ; Models, Animal ; Neurodegenerative Diseases ; Neurogenesis ; Parkinson Disease ; Plaque, Amyloid ; Sonication ; Therapeutic Uses ; Transducers ; Ultrasonography ; United States Food and Drug Administration

Magnetic resonance-guided focused ultrasound (MRgFUS) is a new emerging neurosurgical procedure applied in a wide range of clinical fields. It can generate high-intensity energy at the focal zone in deep body areas without requiring incision of soft tissues. Although the effectiveness of the focused ultrasound technique had not been recognized because of the skull being a main barrier in the transmission of acoustic energy, the development of hemispheric distribution of ultrasound transducer phased arrays has solved this issue and enabled the performance of true transcranial procedures. Advanced imaging technologies such as magnetic resonance thermometry could enhance the safety of MRgFUS. The current clinical applications of MRgFUS in neurosurgery involve stereotactic ablative treatments for patients with essential tremor, Parkinson's disease, obsessive-compulsive disorder, major depressive disorder, or neuropathic pain. Other potential treatment candidates being examined in ongoing clinical trials include brain tumors, Alzheimer's disease, and epilepsy, based on MRgFUS abilities of thermal ablation and opening the blood-brain barrier. With the development of ultrasound technology to overcome the limitations, MRgFUS is gradually expanding the therapeutic field for intractable neurological disorders and serving as a trail for a promising future in noninvasive and safe neurosurgical care.
Acoustics ; Alzheimer Disease ; Blood-Brain Barrier ; Brain Neoplasms ; Depressive Disorder, Major ; Epilepsy ; Essential Tremor ; High-Intensity Focused Ultrasound Ablation ; Humans ; Magnetic Resonance Imaging ; Nervous System Diseases ; Neuralgia ; Neurosurgery* ; Neurosurgical Procedures ; Obsessive-Compulsive Disorder ; Parkinson Disease ; Skull ; Thermometry ; Transducers ; Ultrasonography*

The concept of focused ultrasound (FUS) and its application in the field of medicine have been suggested since the mid-20th century. However, the clinical applications of this technique in central nervous system (CNS) diseases have been extremely limited because the skull inhibits efficient energy transmission. Therefore, early application of FUS treatment was only performed in patients who had already undergone invasive procedures including craniectomy and burr hole trephination. In the 1990s, the phased array technique was developed and this enabled the focus of ultrasonic energy through the skull, and in conjunction with another technique, magnetic resonance thermal monitoring, the possibility of applying FUS in the CNS was further strengthened. The first clinical trial using FUS treatment for CNS diseases was performed in the early 21(st) century in patients with glioblastoma, which consists of highly malignant primary brain tumors. However, this trial resulted in a failure to make lesions in the tumors. Various causes were suggested for this outcome including different acoustic impedances across heterogeneous intracranial tissue (not only brain tissue, but also fibrous or tumor tissue). To avoid the influence of this factor, the targets for FUS treatment were shifted to functional diseases such as essential tremor, Parkinson's disease, and psychiatric disease, which usually occur in normal brain structures. The first trial for functional diseases was started in 2010, and the results were successful as accurate lesions were made in the target area. Nowadays, the indication of FUS treatment for functional CNS diseases is gradually widening, and many trials using the FUS technique are reporting good results. In addition to the lesioning technique using high intensity FUS treatment, the possibility of clinical application of low intensity FUS to CNS disease treatment has been investigated at a preclinical level, and it is expected that FUS treatment will become one of the most important novel techniques for the treatment of CNS diseases in the near future.
Acoustics ; Brain ; Brain Neoplasms ; Central Nervous System Diseases ; Central Nervous System* ; Essential Tremor ; Glioblastoma ; Humans ; Parkinson Disease ; Skull ; Trephining ; Ultrasonics ; Ultrasonography*

A burnt-out prostate cancer tumor is a very rare clinical entity. The term 'burnt-out' refers to a primary tumor that has spontaneously and nearly completely regressed without treatment. Since metastasis of prostate cancer is usually encountered in the presence of advanced disease, distant metastasis with an undetectable primary tumor is very rare. We report herein a case of a burnt-out prostate cancer tumor that metastasized to the thoracic (T) spine and caused cord compression. A 66-year-old man visited the Emergency Department due to weakness of both legs for the past two days. His blood and urine tests were normal at the time. His spine magnetic resonance imaging (MRI) scans looked like bone metastasis that involved the T-7 vertebral body and a posterior element, and caused spinal cord compression. Other images, including from the brain MRI, neck/chest/abdomino-pelvic computed tomography (CT) scan and 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) and endoscopy, revealed no lesions that suggested malignancy. After total corpectomy T-7 and screw fixation/fusion at T5 to T10, the pathology report revealed a metastatic carcinoma that was strongly positive for prostate-specific antigen (PSA). The serum PSA value was 1.5 ng/mL. The transrectal 12-core prostate biopsy and ultrasonography showed no definitive hypoechoic lesion, but one specimen had slight (only 1%) adenocarcinoma with a Gleason score of 6 (3+3). The final diagnosis was burned-out prostate cancer with an initial normal PSA value. Although metastatic disease with an unknown primary origin was confirmed, a more aggressive approach in seeking the primary origin could provide a more specific treatment strategy and greater clinical benefit to patients.
Adenocarcinoma ; Aged ; Biopsy ; Brain ; Diagnosis ; Emergencies ; Endoscopy ; Humans ; Leg ; Magnetic Resonance Imaging ; Neoplasm Grading ; Neoplasm Metastasis ; Pathology ; Prostate* ; Prostate-Specific Antigen ; Prostatic Neoplasms* ; Spinal Cord Compression ; Spine ; Ultrasonography

OBJECTIVE: We wanted to evaluate the clinical value of intraoperative ultrasonography for real-time guidance when performing microneurosurgical resection of small subcortical lesions. MATERIALS AND METHODS: Fifty-two patients with small subcortical lesions were involved in this study. The pathological diagnoses were cavernous hemangioma in 25 cases, cerebral glioma in eight cases, abscess in eight cases, small inflammatory lesion in five cases, brain parasite infection in four cases and the presence of an intracranial foreign body in two cases. An ultrasonic probe was sterilized and lightly placed on the surface of the brain during the operation. The location, extent, characteristics and adjacent tissue of the lesion were observed by high frequency ultrasonography during the operation. RESULTS: All the lesions were located in the cortex and their mean size was 1.3 +/- 0.2 cm. Intraoperative ultrasonography accurately located all the small subcortical lesions, and so the neurosurgeon could provide appropriate treatment. Different lesion pathologies presented with different ultrasonic appearances. Cavernous hemangioma exhibited irregular shapes with distinct margins and it was mildly hyperechoic or hyperechoic. The majority of the cerebral gliomas displayed irregular shapes with indistinct margins, and they often showed cystic and solid mixed echoes. Postoperative imaging identified that the lesions had completely disappeared, and the original symptoms of all the patients were significantly alleviated. CONCLUSION: Intraoperative ultrasonography can help accurately locate small subcortical lesions and it is helpful for selecting the proper approach and guiding thorough resection of these lesions.
Adolescent ; Adult ; Aged ; Brain Diseases/*surgery/ultrasonography ; Brain Neoplasms/surgery/ultrasonography ; Female ; Glioma/surgery/ultrasonography ; Hemangioma, Cavernous, Central Nervous System/surgery/ultrasonography ; Humans ; Male ; *Microsurgery ; Middle Aged ; *Ultrasonography, Interventional ; Young Adult

BACKGROUNDThe goal of surgery in the treatment of intrinsic cerebral tumors is to resect the maximum tumor volume, and to spare the eloquent areas. However, it is difficult to discover the eloquent areas intraoperatively due to individual anatomo-functional variability both for sensori-motor and language functions. Consequently, the surgery of intrinsic cerebral tumors frequently results in poor extent of resection or permanent postoperative deficits, or both, and remains a difficult problem for neurosurgeons.

METHODSFrom January 2003 to January 2010, 112 patients with neuroepithelial tumors in/close to the eloquent areas were operated on under awake anesthesia with the intraoperative direct electrical stimulation for functional mapping of the eloquent areas. The extent of the tumors was verified by intraoperative ultrasonography. The maximal resection of the tumors and minimal damage of the eloquent areas were the surgical goal of all patients.

RESULTSTotally 356 cortical sites in 99 patients were detected for motor response by intraoperative direct electrical stimulation, 50 sites in 16 patients for sensory, 72 sites in 48 patients for language. Sixty-six patients (58.9%) achieved total resection, 34 (30.4%) subtotal and 12 (10.7%) partial. Fifty-eight patients (51.8%) had no postoperative deficit, while 37 patients (33.0%) had transitory postoperative paralysis, 26 patients (23.2%) with transitory postoperative language disturbance and 3 patients (2.7%) with permanent neurological deficits. No patient complained of pain recollection following operation.

CONCLUSIONSAwake anesthesia, intraoperative direct electrical stimulation and ultrasonography are three core techniques for the resection of intrinsic cerebral tumors near the eloquent areas. This new concept allows an improvement in the quality of surgery for neuroepithelial tumors in/adjacent to eloquent areas.

Adolescent ; Adult ; Aged ; Anesthesia ; methods ; Brain Mapping ; methods ; Brain Neoplasms ; diagnostic imaging ; surgery ; Deep Brain Stimulation ; methods ; Female ; Humans ; Male ; Middle Aged ; Neoplasms, Neuroepithelial ; diagnostic imaging ; surgery ; Ultrasonography

Tuberous sclerosis(TS), a type of neurocutaneous syndrome, is inherited in an autosomal dominant manner. Approximately 60% of children with TS have rhabdomyomas of the heart, and 40% of fetuses in whom rhabdomyomas are detected by a prenatal ultrasonography eventually end up with TS. Therefore, when multiple cardiac rhabdomyomas are detected by a fetal ultrasonography, TS should be suspected and further examination should be considered after birth. Infantile spasms is a common type of seizure among young children with TS. We describe a patient with TS who showed cardiac tumors on a fetal ultrasound. Also, hypomelanotic macules, retinal tumors, brain cortical tubers, nodules in subependymal regions, and infantile spasms was detected after birth.
Brain ; Child ; Fetus ; Heart ; Heart Neoplasms ; Humans ; Infant ; Infant, Newborn ; Neurocutaneous Syndromes ; Parturition ; Retinal Neoplasms ; Rhabdomyoma ; Seizures ; Spasms, Infantile ; Tuberous Sclerosis ; Ultrasonography, Prenatal

Hyperthyroidism is seen in 3.5-26% of subjects with acromegaly. Hyperthyroidism can be developed by thyroid stimulating hormone (TSH) dependent mechanism in TSH-secreting adenomas with acromegaly or by TSH independent mechanism through the stimulation of thyroid cells by growth hormone (GH). So, confirming the cause of hyperthyroidism is important to treat that. We report a case of a 56-year-old man who had acromegaly with iodine-induced thyrotoxicosis. He took the sea tangle for 4 years because he had constipation. His face and hands indicated acromegaly. Thyroid function test showed that T3 and free T4 were increased and TSH was decreased. Ultrasonography of neck showed diffuse enlargement of thyroid gland and thyroid scan showed decreased uptake of thyroid gland. So we could confirm iodine-induced thyrotoxicosis due to excessive iodine intake. Serum GH and insulin-like growth factor (IGF)-1 were markedly increased and brain MRI showed heterogenous 1 cm sized pituitary mass in right side. Acromegaly was confirmed by brain MRI, pituitary stimulation test and increased level of GH, IGF-1. He stopped iodine intake. After 6 months, T3, free T4 and TSH were normalized and he is waiting for the surgical removal of pituitary adenoma.
Acromegaly* ; Adenoma ; Brain ; Constipation ; Growth Hormone ; Hand ; Humans ; Hyperthyroidism ; Insulin-Like Growth Factor I ; Iodine ; Magnetic Resonance Imaging ; Middle Aged ; Neck ; Pituitary Neoplasms ; Thyroid Function Tests ; Thyroid Gland ; Thyrotoxicosis* ; Thyrotropin ; Ultrasonography

BACKGROUND: Cheiro-oral-pedal syndrome is characterized by a unilateral or bilateral sensory disturbance in mouth corner and hand and/or foot, and associated with central nervous system disease. Causative diseases are cerebral infarction, intracranial hemorrhage, brain tumor, migraine, etc. When related with cerebral infarction, it is known to have lacunar type pathology and favorable prognosis. But other pathogenic mechanism and poor prognosis is suggested. METHODS: We retrospectively studied 12 patients presented with cheiro-oral-pedal syndrome, who visited the department of neurology in Chosun University Hospital from September 2000 to August 2002. Cheiro-oral-pedal syndrome was diagnosed according to the clinical manifestations and brain MRI findings. We assessed neurological findings, brain MRI and MRA findings, duplex sonographic findings, risk factors of stroke and outcome of the patients. Followup period was 3-20 (mean 8) months. RESULTS: There were 12 patients (10 men, 2 women) with the age ranged from 45 to 80 (mean 57.8) years. Sensory loss on cheiro-oral area was present in 8 (66.7%) and on cheiro-oral-pedal area in 4 (33.3%). Responsible lesions were found in thalamus, capsulo-striatum, corona radiata, pons, and fronto-parietal cortex. Three patients had a major cerebral vascular abnormality on MRA. One had MCA stenosis, the other PCA stenosis and another distal ICA stenosis. Sensory symptoms had remained in all patient except one. In-hospital mortality and other neurological deficit at discharge were absent in all. CONCLUSIONS: Cheiro-oral syndrome has mixed pathogenic mechanism of small vessel disease and large vessel atherosclerosis and involves various sites. Paresthesia itself has bad prognosis but overall clinical course is benign.
Atherosclerosis ; Brain ; Brain Neoplasms ; Central Nervous System ; Cerebral Infarction ; Constriction, Pathologic ; Follow-Up Studies ; Foot ; Hand ; Hospital Mortality ; Humans ; Intracranial Hemorrhages ; Magnetic Resonance Imaging* ; Male ; Migraine Disorders ; Mouth ; Neurology ; Paresthesia ; Passive Cutaneous Anaphylaxis ; Pathology ; Pons ; Prognosis ; Retrospective Studies ; Risk Factors ; Stroke ; Thalamus ; Ultrasonography

Fever of unknown origin (FUO) is caused by infections (30-40%), neoplasms (20-30%), collagen vascular diseases (10-20%), and numerous miscellaneous diseases (15-20%). The literatures also reveal that 5-15% of FUO cases defy diagnosis, despite extensive studies. Diagnostic advances continuously modify the spectrum of FUO-causing diseases. Modern imaging techniques (e.g., ultrasound, CT scan, MRI) enable early detection of abscesses and solid tumors that used to be difficult to diagnose. But the correct diagnosis can be delayed because the tumor, such as rare hematologic malignancy, is difficult to be detected by various imaging studies. Intravascular lymphomatosis (IVL) is a rare form of non-Hodgkin's lymphoma and generally fatal disease characterized by extensive proliferation of neoplastic mononuclear cells within the lumina of blood vessels. The prognosis is usually extremely poor, with rapid death despite chemotherapy. The diagnosis is most frequently made after biopsy of skin or brain but is often established post mortem. Most patients with IVL present with FUO and nonspecific cutaneous and neurologic manifestations. Peripheral nerve system or pulmonary involvements are not common as initial menifestations. We report a case of intravascular lymphomatosis, presenting as FUO with peripheral polyneuropathy. We made early diagnosis of IVL by video-assisted thoracoscopic lung biopsy. She is improving with good performance after the 4th cycle of chemotherapy till now.
Abscess ; Biopsy ; Blood Vessels ; Brain ; Collagen ; Diagnosis ; Drug Therapy ; Early Diagnosis ; Fever of Unknown Origin* ; Fever* ; Hematologic Neoplasms ; Humans ; Lung ; Lymphoma ; Lymphoma, Non-Hodgkin ; Neurologic Manifestations ; Peripheral Nerves ; Polyneuropathies* ; Prognosis ; Skin ; Tomography, X-Ray Computed ; Ultrasonography ; Vascular Diseases