Focused versus conventional radiotherapy in spinal oncology: is there any difference in fusion rates and pseudoarthrosis?

INTRODUCTION: Radiotherapy is considered standard of care for adjuvant peri-operative treatment of many spinal tumors, including those with instrumented fusion. Unfortunately, radiation treatment has been linked to increased risk of pseudoarthrosis. Newer focused radiotherapy strategies with enhanced conformality could offer improved fusion rates for these patients, but this has not been confirmed. METHODS: We performed a retrospective analysis of patients at three tertiary care academic institutions with primary and secondary spinal malignancies that underwent resection, instrumented fusion, and peri-operative radiotherapy. Two board certified neuro-radiologists used the Lenke fusion score to grade fusion status at 6 and 12-months after surgery. Secondary outcomes included clinical pseudoarthrosis, wound complications, the effect of radiation timing and radiobiological dose delivered, the use of photons versus protons, tumor type, tumor location, and use of autograft on fusion outcomes. RESULTS: After review of 1252 spinal tumor patients, there were 60 patients with at least 6 months follow-up that were included in our analyses. Twenty-five of these patients received focused radiotherapy, 20 patients received conventional radiotherapy, and 15 patients were treated with protons. There was no significant difference between the groups for covariates such as smoking status, obesity, diabetes, intraoperative use of autograft, and use of peri-operative chemotherapy. There was a significantly higher rate of fusion for patients treated with focused radiotherapy compared to those treated with conventional radiotherapy at 6-months (64.0% versus 30.0%, Odds ratio: 4.15, p = 0.036) and 12-months (80.0% versus 42.1%, OR: 5.50, p = 0.022). There was a significantly higher rate of clinical pseudoarthrosis in the conventional radiotherapy cohort compared to patients in the focused radiotherapy cohort (19.1% versus 0%, p = 0.037). There was no difference in fusion outcomes for any of the secondary outcomes except for use of autograft. The use of intra-operative autograft was associated with an improved fusion at 12-months (66.7% versus 37.5%, OR: 3.33, p = 0.043). CONCLUSION: Focused radiotherapy may be associated with an improved rate of fusion and clinical pseudoarthrosis when compared to conventional radiation delivery strategies in patients with spinal tumors. Use of autograft at the time of surgery may be associated with improved 12-month fusion rates. Further large-scale prospective and randomized controlled studies are needed to better stratify the effects of radiation delivery modality in these patients.

Neuroradiology in Transgender Care: Facial Feminization, Laryngeal Surgery, and Beyond.

Transgender individuals experience incongruence between their gender identity and the sex assigned to them at birth. This incongruence can cause many transgender individuals to experience distressing physical and mental discord, a diagnosis known as gender dysphoria. Craniofacial structures have distinct anthropometric characteristics that affect perceived masculinity and femininity. The face, neck, and voice are highly exposed anatomic areas that have recognizable gender-specific characteristics that may hinder a transgender individual's successful social integration and public acceptance. Reconstructive facial and laryngeal procedures are among the surgical options transgender persons may elect to undergo to better align their physical appearance with their gender identity. These include feminization surgeries such as facial feminization and reduction chondrolaryngoplasty, as well as masculinizing facial and laryngeal surgeries. Maxillofacial CT is frequently used in the preoperative evaluation of patients before facial feminization surgery (FFS). Several CT measurements guide surgeons to the optimal correction required in FFS to achieve appropriate aesthetic planes. Mapping important craniofacial landmarks to avoid untoward surgical complications is crucial. Transgender patients may encounter other neurologic complications that require neuroimaging evaluation. For example, gender-affirming hormone therapy (eg, estrogen and testosterone) may increase the risk of stroke or may influence growth of various hormone-sensitive tumors such as pituitary adenomas. Radiologists may interpret imaging examinations in transgender patients for routine care or for evaluation before and after facial and laryngeal surgeries and must be aware of the role of neuroimaging in the care of this population. An invited commentary by Callen is available online. The online slide presentation from the RSNA Annual Meeting is available for this article. ©RSNA, 2022.

Treatment of CSF1R-Related Leukoencephalopathy: Breaking New Ground.

BACKGROUND: Colony-stimulating factor-1 receptor (CSF1R)-related leukoencephalopathy is a rapidly progressive neurodegenerative disease for which there is currently no cure. Hematopoietic stem cell transplantation (HSCT) has been proposed as a disease-modifying treatment. OBJECTIVE: The objective of this study was to determine the effect of HSCT on disease progression. METHODS: We collected all available clinical data from a cohort of 7 patients with CSF1R-related leukoencephalopathy who underwent HSCT at our institutions. Clinical data included detailed neurological examination by a board-certified neurologist, serial cognitive screens, formal neuropsychological evaluations, and serial brain magnetic resonance imaging (MRI). RESULTS: Our patients had an average disease duration of 27.6 months at the time of transplant, and we have 87 months of total posttransplant follow-up time (median, 11; range, 2-27). One patient died in the periprocedural period. The remaining patients showed a variable response to treatment, with 6 of 7 patients trending toward stabilization on motor examination, cognitive scores, and/or MRI abnormalities, especially with white matter lesion burden. CONCLUSIONS: This is the largest series of patients with CSF1R-related leukoencephalopathy receiving HSCT. We conclude that HSCT can stabilize the disease in some patients. Variability in patient responsiveness suggests that measures of disease heterogeneity and severity need to be considered when evaluating a patient's candidacy for transplant. HSCT appears to be the first disease-modifying therapy for CSF1R-related leukoencephalopathy. This milestone may serve as a foothold toward better understanding the disease's pathomechanism, thus providing new opportunities for better disease-specific therapies. © 2021 International Parkinson and Movement Disorder Society.

SLC20A2 and THAP1 deletion in familial basal ganglia calcification with dystonia.

Idiopathic basal ganglia calcification (IBGC) is characterized by bilateral calcification of the basal ganglia associated with a spectrum of neuropsychiatric and motor syndromes. In this study, we set out to determine the frequency of the recently identified IBGC gene SLC20A2 in 27 IBGC cases from the Mayo Clinic Florida Brain Bank using both Sanger sequencing and TaqMan copy number analysis to cover the complete spectrum of possible mutations. We identified SLC20A2 pathogenic mutations in two of the 27 cases of IBGC (7 %). Sequencing analysis identified a p.S113* nonsense mutation in SLC20A2 in one case. TaqMan copy number analysis of SLC20A2 further revealed a genomic deletion in a second case, which was part of a large previously reported Canadian IBGC family with dystonia. Subsequent whole-genome sequencing in this family revealed a 563,256-bp genomic deletion with precise breakpoints on chromosome 8 affecting multiple genes including SLC20A2 and the known dystonia-related gene THAP1. The deletion co-segregated with disease in all family members. The deletion of THAP1 in addition to SLC20A2 in the Canadian IBGC family may contribute to the severe and early onset dystonia in this family. The identification of an SLC20A2 genomic deletion in a familial form of IBGC demonstrates that reduced SLC20A2 in the absence of mutant protein is sufficient to cause neurodegeneration and that previously reported SLC20A2 mutation frequencies may be underestimated.

Designing a safer radiology department.

OBJECTIVE: Patients presume safety in radiologic services, but the potential to do harm exists in every area of imaging. Radiology department personnel need to understand basic regulatory requirements for safety and how to promote and improve safety in the future. CONCLUSION: This article reviews key safety metrics that we think are relevant to radiology and discusses how to define the measures and how we are attempting to translate the metrics into a culture of safety.

MR imaging of brainstem atrophy in progressive supranuclear palsy.

BACKGROUND: To enhance the sensitivity and specificity of the clinical diagnosis of progressive supranuclear palsy (PSP), neuroradiological parameters established in pathologically proven cases are needed. METHODS: We examined brainstem atrophy in five pathologically confirmed PSP patients (three men, mean age at death 77 years, range 64-84 years). Time interval between symptom onset and MRI ranged from 1 to 5 years, and between MRI and death from 33 to 52 months. Only one patient had clinical diagnosis of PSP at the time of MRI. Control group consisted of 19 age- and gender-matched healthy subjects. Seventeen morphometric parameters of the midbrain and pons were measured on T1-weighted midsagittal and T2-weighted axial MRI scans with Image Analyzer. Measurements of superior cerebellar peduncle (SCP) width were performed on PSP autopsy specimens. RESULTS: Mean SCP width on MRI in PSP (2.7 +/- 0.8 mm, 95%CI: 2.1-3.3) was smaller than in controls (3.7 +/- 0.5 mm, 95%CI: 3.5-3.9). Mean SCP width at autopsy was 8% smaller than mean SCP width on MRI. Midsagittal midbrain area in PSP (99.1 +/- 6.9 mm(2), 95%CI: 90.5-107.6) was smaller than in controls (141.0 +/- 18.1 mm(2), 95%CI: 132.2-149.7). Midbrain/pons area ratio in PSP was 1:5 and in controls was 1:4 (p < 0.01). Repeat MRI 17 months later in one PSP case revealed 30% decrease of SCP width. CONCLUSIONS: MR imaging with quantitative analysis may be useful in the diagnosis of early PSP and in monitoring disease course.

Brain injury after cardiopulmonary arrest and its assessment with diffusion-weighted magnetic resonance imaging.

OBJECTIVE: To characterize the frequency and pattern of diffusion-weighted imaging (DWI) abnormalities detected as part of brain magnetic resonance imaging (MRI) and their association with short-term neurologic outcomes in patients successfully resuscitated after cardiopulmonary arrest (CPA). PATIENTS AND METHODS: We retrospectively analyzed a case series of patients who experienced CPA between May 1, 2000, and April 29, 2004, at St Luke's Hospital in Jacksonville, Fla. Eligible patients required treatment by the Code Blue team and had 1 DWI study before discharge or death. Two neuroradiologists jointly classified DWI abnormalities by anatomic location. Outcome was measured by Cerebral Performance Category score. RESULTS: Resuscitation was performed 628 times during the 48-month study period. Of 514 CPA survivors, 18 (3.5%) had MRI studies. The median age was 62 years (interquartile range [IQR], 49-73), and 10 were men. Median code duration was 16 minutes (IQR, 11-19 minutes), and median code-to-scan time was 72 hours (IQR, 28-229 hours). A DWI abnormality was noted in 9 (50%) of 18 patients. Cortical areas (global and regional) were the most common sites of restricted diffusion. Diffusion-weighted imaging abnormalities were present in 7 (70%) of 10 patients with a poor neurologic outcome at discharge. CONCLUSION: Magnetic resonance imaging is performed rarely after survival of CPA. In this study with limited sample size, a greater proportion of patients with normal DWI findings had a good neurologic outcome at the time of hospital discharge vs those with abnormal findings. Prospective studies of early and serial MRI (with DWI) are needed to confirm this association and to clarify the prognostic usefulness of such studies.

ACR Appropriateness Criteria® Cerebrovascular Disease.

Diseases of the cerebral vasculature represent a heterogeneous group of ischemic and hemorrhagic etiologies, which often manifest clinically as an acute neurologic deficit also known as stroke or less commonly with symptoms such as headache or seizures. Stroke is the fourth leading cause of death and is a leading cause of serious long-term disability in the United States. Eighty-seven percent of strokes are ischemic, 10% are due to intracerebral hemorrhage, and 3% are secondary to subarachnoid hemorrhage. The past two decades have seen significant developments in the screening, diagnosis, and treatment of ischemic and hemorrhagic causes of stroke with advancements in CT and MRI technology and novel treatment devices and techniques. Multiple different imaging modalities can be used in the evaluation of cerebrovascular disease. The different imaging modalities all have their own niches and their own advantages and disadvantages in the evaluation of cerebrovascular disease. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Cerebral amyloid angiopathy: CT and MR imaging findings.

Cerebral amyloid angiopathy (CAA) is an important but underrecognized cause of cerebrovascular disorders that predominantly affect elderly patients. CAA results from deposition of beta-amyloid protein in cortical, subcortical, and leptomeningeal vessels. This deposition is responsible for the wide spectrum of clinical symptoms and neuroimaging findings. Many cases of CAA are asymptomatic. However, when cases are symptomatic, patients can present with transient neurologic events, progressive cognitive decline, or potentially devastating intracranial hemorrhage. Computed tomography is the imaging study of choice for evaluation of suspected acute cortical hemorrhage, which may be accompanied by subarachnoid, subdural, or intraventricular hemorrhage. Magnetic resonance imaging is best suited for identification of small or chronic cortical hemorrhages and ischemic sequelae of this disease, exclusion of other causes of acute cortical-subcortical hemorrhage, and assessment of disease progression. Accurate recognition of imaging findings is important in guiding clinical decision making in patients with CAA.

Cerebral peduncle angle: Unreliable in differentiating progressive supranuclear palsy from other neurodegenerative diseases.

INTRODUCTION: The significant symptom overlap between progressive supranuclear palsy (PSP) and other parkinsonian neurodegenerative diseases frequently results in misdiagnosis. However, neuroimaging can be used to quantify disease-related morphological changes and specific markers. The cerebral peduncle angle (CPA) has been shown to differentiate clinically diagnosed PSP from other parkinsonian diseases but this result has yet to be confirmed in autopsy-proven disease. METHODS: Magnetic resonance imaging (MRI) scans were obtained for 168 patients representing 69 medical facilities. Following randomization, the images were divided into two groups (Type 1 and Type 2) based upon midbrain morphological differences. Two readers were blinded and independently measured the CPA of 146 patients with autopsy-proven progressive supranuclear palsy (PSP; n = 54), corticobasal degeneration (n = 16), multiple system atrophy (MSA; n = 11) and Lewy body disease (n = 65). RESULTS: Applying two separate measurement techniques revealed no statistically significant differences in CPA measurements among any study groups regardless of classification measurement approach. The interobserver agreement showed significant differences in measurements using the Type 2 approach. CONCLUSION: Measuring the CPA on MRI is not a reliable way of differentiating among patients with PSP, corticobasal degeneration, MSA, or Lewy body disease.

Hypertrophic olivary degeneration: A clinico-radiologic study.

INTRODUCTION: The frequency and causes of hypertrophic olivary degeneration (HOD) are unknown. We compared the clinical and radiological characteristics of unilateral HOD and bilateral HOD. METHODS: We performed a search of a radiologic report database for patients who were radiologically diagnosed as having HOD. This database includes the patients examined at the Mayo Clinic in Florida and Arizona. We used the search terms "hypertrophic olivary degeneration", "HOD", and "olivary" in the reports recorded from 1995 to 2015. Pertinent medical records and magnetic resonance imaging (MRI) scans of the brain for those with HOD were reviewed retrospectively. RESULTS: We identified 142 MRI studies on 95 cases who had radiologically proven HOD, 39 cases had unilateral HOD and 56 with bilateral HOD. In symptomatic cases, the most common symptom was ataxia. Palatal tremor was observed in almost half of all HOD cases. While cerebrovascular diseases were the most frequent etiology in both types of HOD (n = 24, 62% in unilateral; n = 17, 30% in bilateral), more than half of bilateral HOD cases had an unknown etiology (52%, n = 29), whereas only 13% (n = 5) of the unilateral cases had an unknown etiology (χ(2) test, P < 0.001). The lesions of unilateral HOD had a tendency to improve radiologically over time, whereas those associated with bilateral HOD were likely to worsen (χ(2) test, P < 0.05). CONCLUSIONS: Our study showed that bilateral HOD is more common than unilateral HOD. Half of bilateral HOD cases had no obvious cause and some worsened over time. This may implicate a possible primary neurodegenerative process.

ACR Appropriateness Criteria Low Back Pain.

Most patients presenting with uncomplicated acute low back pain (LBP) and/or radiculopathy do not require imaging. Imaging is considered in those patients who have had up to 6 weeks of medical management and physical therapy that resulted in little or no improvement in their back pain. It is also considered for those patients presenting with red flags raising suspicion for serious underlying conditions, such as cauda equina syndrome, malignancy, fracture, and infection. Many imaging modalities are available to clinicians and radiologists for evaluating LBP. Application of these modalities depends largely on the working diagnosis, the urgency of the clinical problem, and comorbidities of the patient. When there is concern for fracture of the lumbar spine, multidetector CT is recommended. Those deemed to be interventional candidates, with LBP lasting for > 6 weeks having completed conservative management with persistent radiculopathic symptoms, may seek MRI. Patients with severe or progressive neurologic deficit on presentation and red flags should be evaluated with MRI. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (the RAND/UCLA Appropriateness Method and the Grading of Recommendations Assessment, Development, and Evaluation) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances in which evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Different patterns of magnetic resonance imaging atrophy for frontotemporal lobar degeneration syndromes.

BACKGROUND: Frontotemporal lobar degeneration (FTLD) is an uncommon degenerative dementia that presents with focal cognitive and behavioral deficits. OBJECTIVE: To determine the correlation of the different presentations of FTLD with structural neuroimaging findings. DESIGN AND PATIENTS: In a blinded study, we retrospectively evaluated the clinical presentations and magnetic resonance imaging (MRI) patterns of atrophy in 59 patients with FTLD and 26 patients with probable Alzheimer disease at a memory disorders clinic. RESULTS: Analysis of variance revealed a significant difference in the patterns of atrophy in the FTLD and Alzheimer disease groups. Patients with FTLD presenting with altered personal conduct had significant bifrontal atrophy, whereas patients presenting with semantic dementia had significant left temporal and bifrontal atrophy compared with other groups. Disinhibited behavior and hyperphagia correlated with right frontal atrophy, and fluent, anomic aphasia correlated with left temporal atrophy. CONCLUSIONS: We found that the type of clinical presentation of FTLD correlates with specific areas of atrophy. Our method of analysis may be useful to elicit further anatomic-behavioral relationships in degenerative brain disorders.

Heredofamilial brain calcinosis syndrome.

Brain calcinosis syndrome (BCS) usually is defined as bilateral calcium accumulation in the brain parenchyma, primarily in the basal ganglia. More than 50 reported clinical conditions have been associated with BCS. We reviewed clinical, radiological, and genetic features of heredofamilial BCS accompanying all conditions associated with calcium accumulation in the brain reported in English between 1962 and 2003 in MEDLINE. The location, extent, and degree of calcification in the brain show diversity not only among the various disorders but also among patients sharing the same condition. The pathogenesis of BCS is uncertain. More complicated mechanisms may be Involved when brain calcinosis is present but calcium, phosphorus, and parathyroid hormone metabolism abnormalities are absent. We review conditions associated with heredofamilial BCS in which brain calcinosis is nearly uniformly present because such information may be Important to the clinician pursuing an investigative strategy.

Neuroimaging in neuropsychiatry.

Once limited to structural imaging modalities such as CT and MRI,radiographic evaluation of the psychiatric patient now includes more sophisticated functional techniques such as fMRI, MR spectroscopy, and PET. With the increased sensitivity that these new tools bring comes greater complexity. As new imaging techniques continue to transition from research to clinical application, the imaging options and associated complexity will increase. Consultation with neuroradiology colleagues will allow the practicing psychiatrist to evaluate their patients optimally. These techniques will continue to provide insight into the pathophysiology, etiology, diagnosis, treatment, and prognosis of these patients.

Whole-exome sequencing as a diagnostic tool in a family with episodic ataxia type 1.

Complex neurologic phenotypes are inherently difficult to diagnose. Whole-exome sequencing (WES) is a new tool in the neurologist's diagnostic armamentarium. Whole-exome sequencing can be applied to investigate the "diagnostic odyssey" cases. These cases involve patients with rare diseases that likely have a genetic etiology but have failed to be diagnosed by clinical evaluation and targeted gene testing. We describe such a case, a 22-year-old man who had mild intellectual developmental disability and episodes of jerking ataxic movements that affected his whole body. He underwent numerous multidisciplinary and multicentric evaluations throughout his life that failed to establish a clear diagnosis. Following his visit to Mayo Clinic in Jacksonville, Florida, WES was applied for genetic determination of the unknown disorder in the proband and his biological parents and sister. Additional clinical evaluation, magnetic resonance neuroimaging, electromyography, and electroencephalography of the proband were performed to verify the phenotype after the WES results were available. To our knowledge, this is the first report of the application of WES to facilitate the diagnosis of episodic ataxia type 1. This case illustrates that WES supported by clinical data is a useful and time-saving tool in the evaluation of patients with rare and complex hereditary disorders.