Tổng số lượt xem trang

Thứ Tư, 30 tháng 10, 2013

CLOTBUST-HF: Hands-Free Ultrasound and tPA in Acute Stroke


CLOTBUST-HF: Hands-Free Ultrasound and tPA in Acute Stroke


October 25, 2013
 
Intracranial ultrasound treatment using an operator-independent device together with tissue plasminogen activator (tPA) in stroke patients appears to be safe and produced promising recanalization rates, a new study has shown.
The study, published online in Stroke on October 24, was led by Andrew D. Barreto, MD, University of Texas Health Science Center at Houston.
He explained to Medscape Medical Newsthat ultrasound therapy causes the meshwork of fibrin strands within the clot to disperse, thereby allowing better access of tPA to the clot. "We are particularly targeting patients who have clots that are not likely to lyse completely with tPA — those with moderate to severe strokes," Dr. Barreto noted.
"Many smaller studies have been performed with transcranial ultrasound and it does seem to have efficacy in helping to dissolve the clot," he said.
The most cited study is the original CLOTBUST (Combined Lysis of Thrombus in Brain Ischemia With Transcranial Ultrasound and Systemic TPA) study published in 2004 in the New England Journal of Medicine, which showed a recanalization rate of 38% with the combination of ultrasound and tPA vs 13% for those given tPA alone.
However, Dr. Barreto noted that delivery of ultrasound via cranial bone windows requires training for both anatomic localization and waveform recognition, which is considered impractical for large-scale use. "As you have to hold the ultrasound device at the same time as identifying the clot, it is too difficult to train enough people to perform the procedure as an emergency bedside therapeutic," he said.
"Mass expansion of properly trained technicians or clinicians to provide 24/7 stroke coverage to complete a pivotal clinical trial of sonothrombolysis represents a major hurdle," the researchers write in the Strokepaper.
Operator-independent transcranial stroke treatment device. Source: The investigators.
 
"To that end, the development of an operator-independent device that can target the proximal intracranial arteries without specialized neurovascular ultrasound training would make a large-scale, phase 3 clinical trial feasible," they add.
Hands-Free Device
Such a "hands-free" device has now been manufactured by Cerevast Therapeutics, and the current study represents the first-ever exposure of patients with acute stroke to a combination of tPA and this hands-free ultrasound device. "This device has been manufactured so that it can be used without special training and be applied to all stroke patients by just placing it on their heads," Dr. Barreto said.
"It is battery powered and easy to fit. One size fits all, with an adjustable head size and ear position," he explained. "It has been designed so that the probes are positioned in the areas of thinnest bone of the skull: 6 probes on the left and 6 on the right. The device rotates and sequentially fires each probe, thus targeting all the areas of the brain where a large blood clot would be."
For the current study, known as CLOTBUST-Hands Free (CLOTBUST-HF), 20 stroke patients with a median National Institutes of Health Stroke Scale score of 15 received standard-dose intravenous tPA, along with 2-MHz pulsed-wave ultrasound therapy delivered by the CLOTBUST-HF device used for 2 hours.
Sites of occlusion were middle cerebral artery in 14 patients, terminal internal carotid artery in 3 patients, and vertebral artery in 3 patients. All patients tolerated the entire 2 hours of ultrasound treatment, and none developed symptomatic intracerebral hemorrhage. No serious adverse events were related to the study device.
40% Recanalization Rate
At 2 hours, 40% of patients had complete recanalization and 10% had partial recanalization. Middle cerebral artery occlusions demonstrated the greatest complete recanalization rate at 57%. At 90 days, 5 patients (25%) had an excellent outcome, defined as a modified Rankin scale score of 0 to 1.
"The recanalization rate of 40% is in line with that shown in the NEJM paper. But we did not have a control group in this study," Dr. Barreto commented. "At day 90 we had a lower percentage of patients with an excellent outcome than in the previous study, but we only had 20 patients so it is difficult to say much about a clinical outcome."
"This is just a pilot study looking at safety of delivering ultrasound treatment to different areas of the brain. We didn't see any safety issues and the results definitely suggest the approach is feasible," he added.
A phase 3 trial — CLOTBUST-ER — is now underway with the hands-free device. The trial is being conducted in 830 patients from 14 countries, with results expected in 2 to 3 years.

Thứ Hai, 28 tháng 10, 2013

SIÊU ÂM CỘT SỐNG CỔ và DẪN ĐƯỜNG CHÍCH KHỚP



Cervical Spine Sonoanatomy

Identifying the Correct Cervical Spine Level
Martinoli et al 7 first described the sonoanatomic characteristics of C6 and C7 transverse processes (anterior and posterior tubercules). This technique is still the most widely used to assess the cervical root level and facilitate precise cervical nerve root injections and stellate ganglion blocks. The transverse processes at C5, C6, and C7 have different tubercle designs, which allow for precise identification. However, this sonographic identification technique is not the primary choice for other cervical spine injections. Previously, we described two different cervical sonographic identification techniques that can be used for procedures performed in the prone position, targeting the cranio cervical junction or upper cervical levels.1,8 Here we will review all the recommended approaches and when to use each sonographic identification technique.

C6 and C7 Approach
This approach is applicable for patients in either the supine or lateral decubitus position. The C6 transverse process is easily identified in the short-axis transverse view with its characteristic sharp anterior tubercle (Figure 2). The large anterior tubercle of C6 is referred to as the Chassaignac tubercle. The C6 transverse process structure can be easily differentiated from the C7 transverse process, which has a prominent posterior tubercle with either an absent or a rudimentary anterior tubercle (Figure 3). The vertebral artery is unprotected at this level and typically enters the transverse process of C6. Next, the higher cervical spinal levels are identified by moving the transducer cranially (Video 1). As the transducer position progresses cranially, the anterior and posterior tubercles assume similar size characteristics (Figure 4) that have been referred to as the “two-humped camel sign.”9



Occiput, C1, and C2 Approach
This approach is applicable for patients in either the prone or lateral decubitus position. We recommend using this approach especially for upper cervical procedures, including greater and third occipital nerve blocks, the C1–2 joint, cervical facet injection, and cervical medial branch blocks.
The transition from the occiput to C1 and C2 can be recognized by using either the long- or short-axis view depending on the planned procedure. 1 We use the short-axis (transverse) view for occipital nerve blocks and C1–2 joint injections and the long-axis view mainly for cervical facet joints and medial branch blocks.

Long-Axis View
The transducer is applied over the midline to obtain a long-axis view of the spine. The occiput, C1 (no or rudimentary spinous process), and C2 can be easily identified (Figure 5).



Short-Axis View
The transducer is applied over the occipital area to obtain a short-axis view. First the occipital bone is identified, and by moving the transducer caudally, the C1 arch is identified (Video 2) and then the first bifid spinous process, which belongs to C2 (Figure 6). Once the C2 spinous process is identified, the transducer is moved laterally (Video 2) to first visualize the lamina, and then the articular pillar of C2 appears. From this position, consecutive articular pillars can be identified by moving the transducer caudally.



Mastoid, C1, and C2 Approach
This approach is applicable only for patients in the lateral decubitus position. We recommend using this approach especially for unilateral upper cervical procedures, including C2–3 joint injection, cervical facet injection, and cervical medial branch blocks. This approach was first described by Eichenberger et al 10 and later adopted by many other investigators.
With the patient in the lateral decubitus position, the transducer is applied just caudal to the mastoid process and perpendicular to the lateral aspect of the neck. The mastoid process, the transverse process of C1, and the vertebral artery will be visible in the view (Figure 7). Moving the transducer slightly caudally, the vertebral artery can be followed as it disappears in the transverse foramen of C2 (Figure 8). Then, by moving the transducer slightly posteriorly, the first articulation that appears in the view will be the C2–3 joint (Figure 9). From this position, consecutive facet joints are identified by caudally moving the transducer (Figure 10). Video 3 demonstrates the transition from the mastoid process to C1 and C2 and how to identify the C2–3 joint.


Cervical Facet Joint Injections
Anatomy and Biomechanics of the Cervical Facet Joints
Cervical facet (zygapophyseal) joints are diarthrodial joints formed by the superior articular process of one vertebra articulating with the inferior articular process of the vertebrae above at the junction of the lamina and the pedicle.
Each facet joint has a fibrous capsule and is lined by a synovial membrane. The joint also contains varying amounts of adipose and fibrous tissue, forming different types of synovial folds. The angulation of the facet joint increases caudally, being about 45° superior to the transverse plane at the upper cervical level and assuming a more vertical position at the upper thoracic level. The superior articular process also faces more posteromedially at the upper cervical level and changes to a more posterolateral direction at the lower cervical level, with C6 being the most common transition level. 11,12

Excessive facet joint compression and capsular ligament strain have  been implicated in neck pain after whiplash injury. 13 The facet joint and capsule have been shown to contain nociceptive elements, deeming them independent pain generators. Facet joint degeneration is more common in the elderly, and the prevalence of facetogenic pain (pain stemming from the facet joints) in chronic neck pain has been reported to range from 35% to 55%. 14,15

Indications for Cervical Facet Intra-articular Injections

Facet joint–mediated pain cannot be diagnosed on the basis of only clinical examination or radiologic imaging. Cervical facet intra-articular injections have been used in the diagnosis and management of facetogenic pain.16However, evidence for the effectiveness of cervical facet injections in accurately diagnosing facet joint–mediated pain is lacking. 17,18 Cervical medial branch blocks are still considered the reference standards for diagnosing pain stemming from the facet joints. 19
Table 1 summarizes the available literature on sonographically guided cervical facet intra-articular injections.

Sonographically Guided Technique for Cervical Facet Intra-articular Injections

Lateral Short-Axis Approach
We recommend this lateral approach for unilateral single-joint injections. The patient is placed in the lateral decubitus position, and the correct cervical level is identified as mentioned above. A high-frequency linear transducer is used, a short-axis view is obtained, and the superior articular and inferior articular processes forming the facet joint appear as hyperechoic signals with the joint space in between as an anechoic gap (Figure 11). The needle is inserted into the joint space in plane from posterior to anterior under real-time sonographic guidance.20,21 


Lateral Long-Axis Approach
We recommend this lateral approach for unilateral multilevel joint injections, as it allows for multiple facet joints to appear in the same sonographic view. The needle is usually inserted out of plane, which results in a shorter needle trajectory and accordingly is less painful. The patient is placed in the lateral decubitus position, and the correct
cervical level is identified as mentioned above. A high- frequency linear transducer is used, and a long-axis view is obtained by placing the transducer just below the mastoid process (see “Cervical Spine Sonoanatomy” section). The superior articular and inferior articular processes forming the facet joint appear as hyperechoic signals with the joint space in between as an anechoic gap (Figure 10). The nee-
dle is usually inserted into the joint space out of plane under real-time sonographic guidance (Video 4).

Posterior Approach
We described this approach above and recommend it for few reasons 8,22:
1. Multilevel injections can be performed with the same sonographic view and may even use a single needle entry point.
2. Bilateral injections can be performed without the need to change position, as the patient is in the prone position.
3. The needle is inserted in plane from a caudal to cranial direction, which matches the caudal angulation of the cervical facet joint, making it easier for the needle to get into the joint space atraumatically.
A longitudinal sagittal scan is obtained first at the midline to identify the correct cervical level. The C1 spine has no or a rudimentary spinous process, and the first identified spinous process belongs to C2 (see above and Figure 5). A low-resolution curved transducer is usually preferred for its larger footprint, which allows multiple levels to appear in the same view. A longitudinal scan is obtained initially at the midline (spinous process), and then by scanning laterally, one can easily see the lamina, and further laterally, the facet column will appear in the image as the characteristic “saw sign” (Figure 11). To identify the lateral border of the facet column, one can scan even more laterally until the facet joints are no longer in the image and then
come back medially toward the joints. The inferior articular processes of the level above and the superior articular process of the level below appear as hyperechoic signals with the joint space in between as an anechoic gap. The needle is then inserted inferior to the caudal end of the transducer and advanced from caudal to cranial in plane to enter the caudal end of the joint under real-time sonographic guidance (Figure 12). 4,22

Cervical Medial Branch (Facet Nerve) Block Injection
Anatomy of the Third Occipital Nerve
The C3 dorsal ramus divides into superficial medial and deep medial branches. The superficial medial branch of C3, also called the third occipital nerve, innervates the C2–3 joint and is the largest cervical medial branch, with a mean diameter of 1.5 mm. The third occipital nerve initially curves around the superior articular process of C3 and then progresses cranially to cross over the C2–3 facet joint and terminates in the suboccipital region. The nerve is offset approximately 1 mm away from bony surface of the C2–3 facet joint. 23 Pain from the C2–3 facet joint often causes cervicogenic headaches and presents with pain in the suboccipital region. The deep medial branch progresses around the C3 articular pillar and is involved with the C4 medial branch in providing innervation to the C3–4 zygapophysial joint. Pain originating from the C2–3 facet joint can be addressed by blocking the ipsilateral third occipital nerve as it crosses the C2–3 facet joint. Pain derived from joints below C2–3 can be addressed by blocking the cervical medial branches as they pass around the waists of the articular pillars. 24

Anatomy of the Medial Branches Innervating the C4–C7 Facet Joints
The C4–C7 dorsal rami arise from their respective spinal nerves and pass dorsally over the root of their corresponding transverse process. The medial branches of the cervical dorsal rami curve medially, around the corresponding articular pillars, and are bound to the periosteum by an investing fascia and held in place by the tendon of the semispinalis capitis muscle. 25 The medial branches for these lower cervical levels are all so typically offset from the bony articular pillar by approximately 1 mm. Each cervical facet joint from C4 through C7 is innervated by two medial branches: the medial branches originating cranially and caudally to the joint. For example the C5–6 facet joint is
innervated by the C5 and C6 medial branches.

Sonographically Guided Third Occipital Nerve and Cervical Medial Branch Blocks
Table 2 summarizes the available literature on sonographically guided third occipital nerve and cervical medial branch blocks.
Sonographically Guided Technique for the Third Occipital Nerve
We will describe a practical step-by-step approach to help perform a precise procedure. The patient is placed in the lateral decubitus position, and a high-frequency linear transducer is applied, just caudal to the mastoid process and perpendicular to the lateral aspect of the neck. The mastoid process, the transverse process of C1, and the vertebral artery will be visible in the view (Figures 7 and 8). Moving the transducer slightly caudally, the vertebral artery can be followed between C1 and C2 as it disappears in the transverse foramen of C2. Then, after moving the transducer slightly posteriorly, the first articulation appearing in the view will be the C2–3 joint (Figure 9). It appears as a convex density made by the inferior articulate process
of C2 (cranial) and the superior articular process on C3 (caudal). The apex of the convexity of the joint represents the joint space, and the third occipital nerve is identified by the typical sonomorphologic appearance of a small peripheral nerve just lateral to the C2–3 joint (Figure 13). This target is kept in the middle of the screen, and the needle is advanced toward the third occipital nerve usually in an out-of-plane approach (Video 5).

Sonographically Guided Technique for Cervical Medial Branch Blocks
The patient is placed in the lateral decubitus position, and a high-frequency linear transducer is applied longitudinally with its upper end just below the mastoid process to obtain a longitudinal view of the cervical spine. Once the C2–3 joint is identified as above, the transducer is slowly moved in a caudal direction to view the lower facet joints until the desired level of the cervical facet joint is reached (Figure 10). The highest points in the bony reflection of the articular pillars represent the facet articulations, and the medial branches can be visualized at the deepest point over the articular pillars between the two articulations (Figure 10), in contrast to the third occipital nerve, which runs over the highest point of the articulation. The needle can be introduced into the target nerve either in plane or out of  plane under real-time sonographic guidance. It is crucial to use Doppler imaging to help identify and avoid any small vessels, as they can otherwise be confused as the small medial branches (Figure 14).








Alternatively, once the correct level is identified, the transducer is rotated to obtain a short-axis view, and the needle is advanced in plane under sonographic guidance toward the articular pillar (Figure 15 and Video 6). Then the transducer can be rotated to the longitudinal plane, as the nerve is better visualized in this view, and the needle is adjusted as needed to lie closer to the nerve (Video 7). 5,20

Pearls
1. The long-axis view is preferable, as having more than 1 cervical level in the view minimizes the risk of miscounting the cervical level and can facilitate placing more than 1 needle for multiple-level injections with the same view.
2. The long-axis view can better identify the nerves, as they will appear in a cross section as an oval structure with the typical sonographic appearance of a small peripheral nerve (Figure 10). This view is particularly helpful for identifying the medial branches before
RF ablation, as this procedure requires precise needle placement along the targeted nerve.
3. The short-axis view offers better visualization of critical blood vessels as they course anteriorly across the articular pillar on their way to the neuroforamen (Figure 16).
4. We recommend performing preinjection scanning in the short-axis view to identify any blood vessels in the vicinity of the target area, and then the needle can be placed in the same view to avoid such blood vessels (Video 8). Afterward, a long-axis view should be obtained in an effort to identify the actual medial branches, and the needle can be adjusted slightly as needed.
5. Sonographic scanning before the planned procedure can help with the diagnosis and identifying the underlying condition, eg, facet arthritis (Figure 17) or facet joint effusion (Figure 18).

Conclusions
Sonographic guidance for the identification of cervical spinal structures and for the performance of cervical procedures is rapidly evolving. An in-depth understanding of sonoanatomy is critical for procedural success. It is important for practitioners to fully understand the visualization advantages and limitations associated with sonographically guided procedures in comparison to fluoroscopically based techniques. Based on the promising results of sonographically guided third occipital nerve and cervical medial branch blocks, clinical studies are warranted to evaluate the safety and efficacy of the sonographically guided RF technique with direct comparison to a fluoroscopically based method. The future for sonographically guided cervical procedures is bright, and these techniques offer many visual advantages that are not found with fluoroscopically based techniques.