Dorith Goldsher

A prospective evaluation of a protocol for magnetic resonance imaging of patients with implanted cardiac devices

BACKGROUND Magnetic resonance imaging (MRI) is avoided in most patients with implanted cardiac devices because of safety concerns. OBJECTIVE To define the safety of a protocol for MRI at the commonly used magnetic strength of 1.5 T in patients with implanted cardiac devices. DESIGN Prospective nonrandomized trial. (ClinicalTrials.gov registration number: NCT01130896) SETTING: One center in the United States (94% of examinations) and one in Israel. PATIENTS 438 patients with devices (54% with pacemakers and 46% with defibrillators) who underwent 555 MRI studies. INTERVENTION Pacing mode was changed to asynchronous for pacemaker-dependent patients and to demand for others. Tachyarrhythmia functions were disabled. Blood pressure, electrocardiography, oximetry, and symptoms were monitored by a nurse with experience in cardiac life support and device programming who had immediate backup from an electrophysiologist. MEASUREMENTS Activation or inhibition of pacing, symptoms, and device variables. RESULTS In 3 patients (0.7% [95% CI, 0% to 1.5%]), the device reverted to a transient back-up programming mode without long-term effects. Right ventricular (RV) sensing (median change, 0 mV [interquartile range {IQR}, -0.7 to 0 V]) and atrial and right and left ventricular lead impedances (median change, -2 Ω [IQR, -13 to 0 Ω], -4 Ω [IQR, -16 to 0 Ω], and -11 Ω [IQR, -40 to 0 Ω], respectively) were reduced immediately after MRI. At long-term follow-up (61% of patients), decreased RV sensing (median, 0 mV, [IQR, -1.1 to 0.3 mV]), decreased RV lead impedance (median, -3 Ω, [IQR, -29 to 15 Ω]), increased RV capture threshold (median, 0 V, IQR, [0 to 0.2 Ω]), and decreased battery voltage (median, -0.01 V, IQR, -0.04 to 0 V) were noted. The observed changes did not require device revision or reprogramming. LIMITATIONS Not all available cardiac devices have been tested. Long-term in-person or telephone follow-up was unavailable in 43 patients (10%), and some data were missing. Those with missing long-term capture threshold data had higher baseline right atrial and right ventricular capture thresholds and were more likely to have undergone thoracic imaging. Defibrillation threshold testing and random assignment to a control group were not performed. CONCLUSION With appropriate precautions, MRI can be done safely in patients with selected cardiac devices. Because changes in device variables and programming may occur, electrophysiologic monitoring during MRI is essential.

Basilar Vasospasm Diagnosis: Investigation of a Modified “Lindegaard Index” Based on Imaging Studies and Blood Velocity Measurements of the Basilar Artery

Background and Purpose— Numerous studies have shown that cerebral vasospasm is one of the leading causes of death and neurological disability after subarachnoid hemorrhage. Most of these studies, however, have focused on anterior circulation vessels. Since the introduction of the transcranial Doppler (TCD), increasing attention has been given to basilar artery (BA) vasospasm, especially in traumatic subarachnoid hemorrhage. As shown for the anterior circulation, however, the significance of elevated flow velocities (FVs) in the posterior vessels may be ambiguous, so vasospasm may not be reliably differentiated from hyperemia. The purpose of the present study was to evaluate the potential additional value of an intracranial/extracranial FV ratio in the posterior circulation to cope with this shortcoming of the TCD in the diagnosis of BA vasospasm. Methods— FV in the extracranial vertebral artery (VA) was measured in 20 healthy volunteers. Normative values of an intracranial/extracranial VA FV ratio (IVA/EVA) and a BA/extracranial VA FV ratio (BA/EVA) were calculated. Thirty-four patients with subarachnoid hemorrhage were then evaluated with TCD and CT angiography (CTA). The value of the IVA/EVA and BA/EVA ratios in the diagnosis and assessment of vertebrobasilar vasospasm was investigated. Results— The extracranial VA could be insonated in all subjects at depths ranging from 45 to 55 mm. The average FV for the extracranial VA was 26 cm/s. The ratios between intracranial and extracranial VA FVs were 1.6 on both sides, whereas the ratio between the BA FVs and the mean extracranial VA FVs was slightly higher at 1.7. Fourteen patients (41.2%) had CTA evidence of BA vasospasm. Vasospasm was severe in 7 patients, moderate in 1, and mild in the remaining. An FV threshold of 80 cm/s was indicative of BA vasospasm in 92.8% with 3 false-positive results that could be related to vertebrobasilar hyperemia. Comparative analysis between CTA and TCD findings showed that BA/EVA was >2 in all patients with BA vasospasm (100% sensitivity) and <2 in all but 1 patient without BA vasospasm (95% specificity). Furthermore, the BA/EVA ratio showed a close correlation with BA diameter (r =−0.8139, P <0.0001) and was >3 in all patients with severe vasospasm. Conclusions— The results of the present study showed that the BA/EVA ratio may contribute to an improved discrimination between BA vasospasm and vertebrobasilar hyperemia and enhance the accuracy and reliability of TCD in the diagnosis of BA vasospasm. Our data further suggest that the BA/EVA ratio may provide an approximation of vasospasm severity and help in identifying patients who are likely to suffer from hemodynamically significant vasospasm.

MRI Guided Focused Ultrasound Thalamotomy for Moderate-to-Severe Tremor in Parkinson’s Disease

Background. Thalamotomy is effective in alleviating tremor in Parkinsons disease (PD). Methods. Seven PD patients, mean age 59.4 ± 9.8 years (range, 46–74) with a mean disease duration of 5.4 ± 2.8 years (range, 2–10) suffering from severe refractory tremor, underwent ventral intermediate nucleus thalamotomy using MRI guided focused ultrasound (MRgFUS), an innovative technology that enables noninvasive surgery. Results. Tremor stopped in the contralateral upper extremity in all patients immediately following treatment. Total UPDRS decreased from 37.4 ± 12.2 to 18.8 ± 11.1 (p = 0.007) and PDQ-39 decreased from 42.3 ± 16.4 to 21.6 ± 10.8 (p = 0.008) following MRgFUS. These effects were sustained (mean follow-up 7.3 months). Adverse events during MRgFUS included headache (n = 3), dizziness (n = 2), vertigo (n = 4), and lip paresthesia (n = 1) and following MRgFUS were hypogeusia (n = 1), unsteady feeling when walking (n = 1, resolved), and disturbance when walking tandem (n = 1, resolved). Conclusions. Thalamotomy using MRgFUS is safe and effective in PD patients. Large randomized studies are needed to assess prolonged efficacy and safety.

Color-coded duplex ultrasound compared to CT angiography for detection and quantification of carotid artery stenosis

OBJECTIVE The purpose of this study was to compare findings on color-coded duplex ultrasound and CT angiography for grading internal carotid artery stenosis, and to investigate whether both these imaging modalities are necessary for an accurate diagnosis of carotid stenosis in the pre-surgical assessment of the internal carotid artery. PATIENTS AND METHODS We examined 92 internal carotid arteries from 46 randomly chosen patients with suspected carotid stenosis by color-coded duplex ultrasound and by three-dimensional CT angiography (CTA). This retrospective study adhered to international guidelines with gradings of mild, moderate, severe, and occlusive carotid disease. RESULTS The study demonstrated agreement between the degree of stenosis found on color-coded duplex ultrasound and that found on CTA in 78% of cases overall and in 79% of patients requiring surgical intervention. When compared to CTA, color-coded duplex ultrasound yielded a sensitivity of 78.9% and a specificity of 96.3%. Although findings on color-coded duplex ultrasound and CTA were comparable, disagreement affecting treatment decision occurred in 10:92 arteries. CONCLUSION CTA was not found to be beneficial for patients exhibiting mild stenosis on color-coded duplex ultrasound, as none of the mild groupings found by sonography were interpreted as severe or occluded by CTA. However, CTA may be an important adjunct to color-coded duplex ultrasound regarding the categories of moderate, severe and occluded when carotid endarterectomy is considered.

Sacrococcygeal Extradural Ependymoma

A case of lumbosacral extradural myxopapillary ependymoma is reported. The clinical, embryologic, and therapeutic features of this rare lesion are presented. The unusual entity is discussed in the light of previous experience with extradural ependymoma in the lumbosacral region.

Magnetic resonance–guided focused ultrasound thalamotomy for tremor: a report of 30 Parkinson's disease and essential tremor cases

OBJECTIVE Thalamotomy of the ventral intermediate nucleus (VIM) is effective in alleviating medication-resistant tremor in patients with essential tremor (ET) and Parkinsons disease (PD). MR-guided focused ultrasound (MRgFUS) is an innovative technology that enables noninvasive thalamotomy via thermal ablation. METHODS Patients with severe medication-resistant tremor underwent unilateral VIM thalamotomy using MRgFUS. Effects on tremor were evaluated using the Clinical Rating Scale for Tremor (CRST) in patients with ET and by the motor part of the Unified Parkinsons Disease Rating Scale (UPDRS) in patients with PD and ET-PD (defined as patients with ET who developed PD many years later). Quality of life in ET was measured by the Quality of Life in Essential Tremor (QUEST) questionnaire and in PD by the PD Questionnaire (PDQ-39). RESULTS Thirty patients underwent MRgFUS, including 18 with ET, 9 with PD, and 3 with ET-PD. The mean age of the study population was 68.9 ± 8.3 years (range 46-87 years) with a mean disease duration of 12.1 ± 8.9 years (range 2-30 years). MRgFUS created a lesion at the planned target in all patients, resulting in cessation of tremor in the treated hand immediately following treatment. At 1 month posttreatment, the mean CRST score of the patients with ET decreased from 40.7 ± 11.6 to 9.3 ± 7.1 (p < 0.001) and was 8.2 ± 5.0 six months after treatment (p < 0.001, compared with baseline). Average QUEST scores decreased from 44.8 ± 12.9 to 13.1 ± 13.2 (p < 0.001) and was 12.3 ± 7.2 six months after treatment (p < 0.001). In patients with PD, the mean score of the motor part of the UPDRS decreased from 24.9 ± 8.0 to 16.4 ± 11.1 (p = 0.042) at 1 month and was 13.4 ± 9.2 six months after treatment (p = 0.009, compared with baseline). The mean PDQ-39 score decreased from 38.6 ± 16.8 to 26.1 ± 7.2 (p = 0.036) and was 20.6 ± 8.8 six months after treatment (p = 0.008). During follow-up of 6-24 months (mean 11.5 ± 7.2 months, median 12.0 months), tremor reappeared in 6 of the patients (2 with ET, 2 with PD, and 2 with ET-PD), to a lesser degree than before the procedure in 5. Adverse events that transiently occurred during sonication included headache (n = 11), short-lasting vertigo (n = 14) and dizziness (n = 4), nausea (n = 3), burning scalp sensation (n = 3), vomiting (n = 2) and lip paresthesia (n = 2). Adverse events that lasted after the procedure included gait ataxia (n = 5), unsteady feeling (n = 4), taste disturbances (n = 4), asthenia (n = 4), and hand ataxia (n = 3). No adverse event lasted beyond 3 months. Patients underwent on average 21.0 ± 6.9 sonications (range 14-45 sonications) with an average maximal sonication time of 16.0 ± 3.0 seconds (range 13-24 seconds). The mean maximal energy reached was 12,500 ± 4274 J (range 5850-23,040 J) with a mean maximal temperature of 56.5° ± 2.2°C (range 55°-60°C). CONCLUSIONS MRgFUS VIM thalamotomy to relieve medication-resistant tremor was safe and effective in patients with ET, PD, and ET-PD. Current results emphasize the superior adverse events profile of MRgFUS over other surgical approaches for treating tremor with similar efficacy. Large randomized studies are needed to assess prolonged efficacy and safety.

Carboplatin and etoposide for recurrent malignant glioma following surgical and radiotherapy failure: A clinical study conducted at the Northern Israel Oncology Center.

We conducted a phase II study using carboplatin and etoposide on patients with recurrent malignant glioma to investigate tumor response.

Joubert Syndrome in French Canadians and Identification of Mutations in CEP104

Joubert syndrome (JBTS) is a primarily autosomal-recessive disorder characterized by a distinctive mid-hindbrain and cerebellar malformation, oculomotor apraxia, irregular breathing, developmental delay, and ataxia. JBTS is a genetically heterogeneous ciliopathy. We sought to characterize the genetic landscape associated with JBTS in the French Canadian (FC) population. We studied 43 FC JBTS subjects from 35 families by combining targeted and exome sequencing. We identified pathogenic (n = 32 families) or possibly pathogenic (n = 2 families) variants in genes previously associated with JBTS in all of these subjects, except for one. In the latter case, we found a homozygous splice-site mutation (c.735+2T>C) in CEP104. Interestingly, we identified two additional non-FC JBTS subjects with mutations in CEP104; one of these subjects harbors a maternally inherited nonsense mutation (c.496C>T [p.Arg166*]) and a de novo splice-site mutation (c.2572-2A>G), whereas the other bears a homozygous frameshift mutation (c.1328_1329insT [p.Tyr444fs*3]) in CEP104. Previous studies have shown that CEP104 moves from the mother centriole to the tip of the primary cilium during ciliogenesis. Knockdown of CEP104 in retinal pigment epithelial (RPE1) cells resulted in severe defects in ciliogenesis. These observations suggest that CEP104 acts early during cilia formation by regulating the conversion of the mother centriole into the cilia basal body. We conclude that disruption of CEP104 causes JBTS. Our study also reveals that the cause of JBTS has been elucidated in the great majority of our FC subjects (33/35 [94%] families), even though JBTS shows substantial locus and allelic heterogeneity in this population.

Subependymal mass lesions and peripheral polyneuropathy in adult-onset glutaric aciduria type I

Glutaric aciduria type I (GA-I) is an autosomal recessive disease caused by a deficiency of the mitochondrial enzyme glutaryl CoA dehydrogenase (GCDH). This metabolic block causes increased urinary concentrations of glutaric and 3-hydroxyglutaric acids. The accumulation and excretion of glutarylcarnitine esters leads to secondary carnitine deficiency. GA-I has an incidence of 1:30,000. The clinical hallmark of GA-I is an acute encephalopathic crisis, with bilateral striatal necrosis presented by severe dystonic dyskinetic disorder. Most patients have their first symptoms during infancy, but some have a less severe form of the disease and some may even remain asymptomatic.1

Method for rapid MRI needle tracking

A new method for MRI needle tracking within a given two‐dimensional (2D) image slice is presented. The method is based on k‐space investigation of the difference image between the current dynamic frame and a reference frame. Using only a few central k‐lines of the difference image and a nonlinear optimization procedure, one can resolve the parameters that define the 2D sinc function that best characterizes the needle in k‐space. The spatial location and orientation of the needle are determined from these parameters. Rapid needle tracking is obtained by repeated acquisitions of the same set of several central k‐lines (as in a “keyhole” protocol) and repeated computation of these parameters. The calculated needle tip is depicted on the reference image by means of a graphic overlay. The procedure was tested in computer simulations and in actual MRI scans (the computations were done offline). It was demonstrated that six k‐lines out of 128 usually suffice to locate the needle. The refresh rate of the needle location depends on the time required to sample the subset of k‐lines, calculate the current needle location, and refresh the reference image. Magn Reson Med 51:1083–1087, 2004.