Non-functioning pituitary macroadenoma following surgery: long-term outcomes and development of an optimal follow-up strategy.

Objectives: Recurrence and regrowth of non-functioning pituitary macroadenomas (NFPMs) after surgery are common but remain unpredictable. Therefore, the optimal timing and frequency of follow-up imaging remain to be determined. We sought to determine the long-term surgical outcomes of NFPMs following surgery and develop an optimal follow-up strategy. Methods: Patients underwent surgery for NFPMs between 1987 and 2018, with a follow-up of 6 months or more, were identified. Demographics, presentation, management, histology, imaging, and surgical outcomes were retrospectively collected. Results: In total, 383 patients were included; 256 were men (256/383; 67%) with median follow-up of 8 years. Following primary surgery, 229 patients (229/383; 60%) achieved complete resection. Of those, 28 (28/229; 11%) developed recurrence, including six needed secondary surgery (6/229; 3%). The rate of complete resection improved over time; in the last quartile of cases, 77 achieved complete resection (77/95; 81%). Reoperation-free survival at 5, 10 and 15 years was 99%, 94% and 94%, respectively. NFPMs were incompletely resected in 154 patients (154/383; 40%); of those, 106 (106/154; 69%) had regrowth, and 84 (84/154; 55%) required reoperation. Surgical reintervention-free survival at 5, 10 and 15 years was 74%,49% and 35%, respectively. Young age and cavernous sinus invasion were risk factors for undergoing reoperation (P < 0.001 and P < 0.0001, respectively) and radiotherapy (P = 0.003 and P < 0.001, respectively). Patients with residual tumour required reoperation earlier than those underwent complete resection (P = 0.02). Radiotherapy to control tumour regrowth was delivered to 65 patients (65/383; 17%) after median time of 1 year following surgery. Radiotherapy was administered more in patients with regrowth of residual disease (61/106; 58%) than those who had NFPMs recurrence (4/28; 14%) (P ≤ 0.001) Following postoperative radiotherapy, one patient (1/65; 2%) had evidence of regrowth, seven (7/65; 11%) had tumour regression on imaging, and no patients underwent further surgery. Conclusions: NFPMs recurrence and regrowth are common, particularly in patients with residual disease post-operatively. We propose a follow-up strategy based on stratifying patients as "low risk" if there is no residual tumour, with increasing scan intervals, or "high risk" if there is a residual tumour, with annual scans for at least five years and extended lifelong surveillance after that.

HLA-DRB1*1501 influences long-term disability progression and tissue damage on MRI in relapse-onset multiple sclerosis.

BACKGROUND: Whether genetic factors influence the long-term course of multiple sclerosis (MS) is unresolved. OBJECTIVE: To determine the influence of HLA-DRB1*1501 on long-term disease course in a homogeneous cohort of clinically isolated syndrome (CIS) patients. METHODS: One hundred seven patients underwent clinical and MRI assessment at the time of CIS and after 1, 3, 5 and 15 years. HLA-DRB1*1501 status was determined using Sanger sequencing and tagging of the rs3135388 polymorphism. Linear/Poisson mixed-effects models were used to investigate rates of change in EDSS and MRI measures based on HLA-DRB1*1501 status. RESULTS: HLA-DRB1*1501 -positive (n = 52) patients showed a faster rate of disability worsening compared with the HLA-DRB1*1501 -negative (n = 55) patients (annualised change in EDSS 0.14/year vs. 0.08/year, p < 0.025), and a greater annualised change in T2 lesion volume (adjusted difference 0.45 mL/year, p < 0.025), a higher number of gadolinium-enhancing lesions, and a faster rate of brain (adjusted difference -0.12%/year, p < 0.05) and spinal cord atrophy (adjusted difference -0.22 mm2/year, p < 0.05). INTERPRETATION: These findings provide evidence that the HLA-DRB1*1501 allele plays a role in MS severity, as measured by long-term disability worsening and a greater extent of inflammatory disease activity and tissue loss. HLA-DRB1*1501 may provide useful information when considering prognosis and treatment decisions in early relapse-onset MS.

The prognostic significance of early blood neurofilament light chain concentration and magnetic resonance imaging variables in relapse-onset multiple sclerosis.

BACKGROUND: Improved prognostication remains vital in multiple sclerosis to inform personalized treatment approaches. Blood neurofilament light (bNfL) is a promising prognostic biomarker, but to what extent it provides additional information, independent of established MRI metrics, is yet to be established. METHODS: We obtained all available bNfL data for 133 patients from a longitudinal observational cohort study. Patients were dichotomized into good or poor outcome groups based upon clinical and cognitive assessments performed 15 years after a clinically isolated syndrome. We performed longitudinal modeling of early NfL and MRI variables to examine differences between outcome groups. RESULTS: The bNfL dataset was incomplete, with one to three (mean 1.5) samples available per participant. Within 3 months of onset, bNfL was similar between groups. The bNfL concentration subsequently decreased in those with a good outcome, and remained persistently elevated in those with a poor outcome. By year 5, NfL in the poor outcome group was approximately double that of those with a good outcome (14.58 [10.40-18.77] vs. 7.71 [6.39-9.04] pg/ml, respectively). Differences were reduced after adjustment for longitudinal changes in T2LV, but trends persisted for a greater rate of increase in NfL in those with a poor outcome, independent of T2LV. CONCLUSIONS: This analysis requires replication in cohorts with more complete bNfL datasets, but suggests that persistently elevated blood NfL may be more common in patients with a poor long-term outcome. Persistent elevation of blood NfL may provide additional prognostic information not wholly accounted for by standard monitoring techniques.

Performance of the 2017 and 2010 Revised McDonald Criteria in Predicting MS Diagnosis After a Clinically Isolated Syndrome: A MAGNIMS Study.

BACKGROUND AND OBJECTIVES: To compare the performance of the 2017 revisions to the McDonald criteria with the 2010 McDonald criteria in establishing multiple sclerosis (MS) diagnosis and predicting prognosis in patients with clinically isolated syndrome (CIS) suggestive of MS. METHODS: CSF examination and brain and spinal cord MRI obtained ≤5 months from CIS onset and a follow-up brain MRI acquired within 15 months from CIS onset were evaluated in 785 patients with CIS from 9 European centers. Date of second clinical attack and of reaching Expanded Disability Status Scale score (EDSS) ≥3.0, if they occurred, were also collected. Performance of the 2017 and 2010 McDonald criteria for dissemination in space (DIS), dissemination in time (DIT) (including oligoclonal bands assessment), and DIS plus DIT for predicting a second clinical attack (clinically definite MS [CDMS]) and EDSS ≥3.0 at follow-up was evaluated. Time to MS diagnosis for the different criteria was also estimated. RESULTS: At follow-up (median 69.1 months), 406/785 patients with CIS developed CDMS. At 36 months, the 2017 DIS plus DIT criteria had higher sensitivity (0.83 vs 0.66), lower specificity (0.39 vs 0.60), and similar area under the curve values (0.61 vs 0.63). Median time to MS diagnosis was shorter with the 2017 vs the 2010 or CDMS criteria (2017 revision, 3.2; 2010 revision, 13.0; CDMS, 58.5 months). The 2 sets of criteria similarly predicted EDSS ≥3.0 milestone. Three periventricular lesions improved specificity in patients ≥45 years. DISCUSSION: The 2017 McDonald criteria showed higher sensitivity, lower specificity, and similar accuracy in predicting CDMS compared to 2010 McDonald criteria, while shortening time to diagnosis of MS. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that the 2017 McDonald Criteria more accurately distinguish CDMS in patients early after a CIS when compared to the 2010 McDonald criteria.

A 30-Year Clinical and Magnetic Resonance Imaging Observational Study of Multiple Sclerosis and Clinically Isolated Syndromes.

OBJECTIVE: Clinical outcomes in multiple sclerosis (MS) are highly variable. We aim to determine the long-term clinical outcomes in MS, and to identify early prognostic features of these outcomes. METHODS: One hundred thirty-two people presenting with a clinically isolated syndrome were prospectively recruited between 1984 and 1987, and followed up clinically and radiologically 1, 5, 10, 14, 20, and now 30 years later. All available notes and magnetic resonance imaging scans were reviewed, and MS was defined according to the 2010 McDonald criteria. RESULTS: Clinical outcome data were obtained in 120 participants at 30 years. Eighty were known to have developed MS by 30 years. Expanded Disability Status Scale (EDSS) scores were available in 107 participants, of whom 77 had MS; 32 (42%) remained fully ambulatory (EDSS scores ≤3.5), all of whom had relapsing-remitting MS (RRMS), 3 (4%) had RRMS and EDSS scores >3.5, 26 (34%) had secondary progressive MS (all had EDSS scores >3.5), and MS contributed to death in 16 (20%). Of those with MS, 11 received disease-modifying therapy. The strongest early predictors (within 5 years of presentation) of secondary progressive MS at 30 years were presence of baseline infratentorial lesions and deep white matter lesions at 1 year. INTERPRETATION: Thirty years after onset, in a largely untreated cohort, there was a divergence of MS outcomes; some people accrued substantial disability early on, whereas others ran a more favorable long-term course. These outcomes could, in part, be predicted by radiological findings from within 1 year of first presentation. ANN NEUROL 2020;87:63-74.

Early imaging predictors of long-term outcomes in relapse-onset multiple sclerosis.

The clinical course of relapse-onset multiple sclerosis is highly variable. Demographic factors, clinical features and global brain T2 lesion load have limited value in counselling individual patients. We investigated early MRI predictors of key long-term outcomes including secondary progressive multiple sclerosis, physical disability and cognitive performance, 15 years after a clinically isolated syndrome. A cohort of patients with clinically isolated syndrome (n = 178) was prospectively recruited within 3 months of clinical disease onset and studied with MRI scans of the brain and spinal cord at study entry (baseline) and after 1 and 3 years. MRI measures at each time point included: supratentorial, infratentorial, spinal cord and gadolinium-enhancing lesion number, brain and spinal cord volumetric measures. The patients were followed-up clinically after ∼15 years to determine disease course, and disability was assessed using the Expanded Disability Status Scale, Paced Auditory Serial Addition Test and Symbol Digit Modalities Test. Multivariable logistic regression and multivariable linear regression models identified independent MRI predictors of secondary progressive multiple sclerosis and Expanded Disability Status Scale, Paced Auditory Serial Addition Test and Symbol Digit Modalities Test, respectively. After 15 years, 166 (93%) patients were assessed clinically: 119 (72%) had multiple sclerosis [94 (57%) relapsing-remitting, 25 (15%) secondary progressive], 45 (27%) remained clinically isolated syndrome and two (1%) developed other disorders. Physical disability was overall low in the multiple sclerosis patients (median Expanded Disability Status Scale 2, range 0-10); 71% were untreated. Baseline gadolinium-enhancing (odds ratio 3.16, P < 0.01) and spinal cord lesions (odds ratio 4.71, P < 0.01) were independently associated with secondary progressive multiple sclerosis at 15 years. When considering 1- and 3-year MRI variables, baseline gadolinium-enhancing lesions remained significant and new spinal cord lesions over time were associated with secondary progressive multiple sclerosis. Baseline gadolinium-enhancing (ß = 1.32, P < 0.01) and spinal cord lesions (ß = 1.53, P < 0.01) showed a consistent association with Expanded Disability Status Scale at 15 years. Baseline gadolinium-enhancing lesions was also associated with performance on the Paced Auditory Serial Addition Test (ß = - 0.79, P < 0.01) and Symbol Digit Modalities Test (ß = -0.70, P = 0.02) at 15 years. Our findings suggest that early focal inflammatory disease activity and spinal cord lesions are predictors of very long-term disease outcomes in relapse-onset multiple sclerosis. Established MRI measures, available in routine clinical practice, may be useful in counselling patients with early multiple sclerosis about long-term prognosis, and personalizing treatment plans.

Inclusion of optic nerve involvement in dissemination in space criteria for multiple sclerosis.

OBJECTIVE: To investigate the effect of including optic nerve involvement in dissemination in space (DIS) criteria for diagnosis of multiple sclerosis (MS) in patients with clinically isolated syndrome (CIS). METHODS: We studied 160 patients with CIS: 129 with optic neuritis (ON) and 31 with non-ON CIS. MRI brain/spinal cord was done at the time of presentation and a follow-up MRI brain after 3-12 months. We evaluated optic nerve involvement clinically or with visual evoked potentials (VEPs, n = 42). We investigated the performance of the McDonald 2017 DIS criteria and modified DIS criteria including optic nerve involvement for development of clinically definite MS after ∼15 years. RESULTS: In the ON group, including symptomatic optic nerve involvement identified an additional 15 patients with DIS. The modified DIS criteria that included optic nerve involvement were more sensitive (95% vs 83%) and more accurate (81% vs 78%) than the McDonald 2017 DIS criteria, but less specific (57% vs 68%). In combination with dissemination in time criteria, the modified DIS criteria remained more sensitive (83% vs 74%) and accurate (81% vs 75%), and the specificity was the same (77%). Including asymptomatic optic nerve involvement in DIS the non-ON group did not identify any additional patients and the performance of the McDonald 2017 criteria and the modified criteria was the same. CONCLUSION: The inclusion of symptomatic optic nerve involvement in DIS in patients with ON improved the overall performance of MS diagnostic criteria. Including asymptomatic optic nerve involvement in DIS in patients with a non-ON CIS may be of limited value. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with suspected MS, inclusion of symptomatic optic nerve involvement in DIS criteria improves the overall performance of diagnostic criteria for MS.

Stroke-induced resolution of primary blepharospasm: evidence for the lenticular nucleus as a control candidate.

Primary blepharospasm is an adult-onset focal dystonia characterised by involuntary contractions of the orbicularis oculi, leading to bilateral spasmodic closure of the eyelids. While spasms of this muscle constitute the hallmark of disease, other motor manifestations include increased spontaneous blinking and apraxia of eyelid opening. Originally misdiagnosed as a psychiatric condition, blepharospasm is now well established as being of neurological origin although questions remain as to its pathophysiological mechanisms.We report a 66-year-old woman who had a 14-year history of primary blepharospasm which completely resolved following a left medial cerebral artery thromboembolic infarct of the lenticular nucleus. This report provides supporting evidence of the lenticular nucleus as a key structure mediating the disease which can lead to functional blindness.

Imaging Investigation of Thyroid Eye Disease.

INTRODUCTION: Thyroid eye disease (TED), is a term referring to the extrathyroidal manifestation of Grave's disease, a disorder which is currently the most common cause of hyperthyroidism and is characterised by underlying autoimmunity.The pathogenic course of the disease can be broadly classified into two stages, an early inflammatory and a late fibrotic stage. These stages are reflected in clinical severity and activity classifications, such as Clinical Activity Score and Class 0: No signs or symptoms, 1: Only signs, no symptoms (e. g. lid retraction), 2: Soft tissue involvement, 3: Proptosis, 4: Extraocular muscle involvement, 5: Corneal involvement, 6: Sight loss (NOSPECS). Classifications based on the latter, have important implications in treatment decisions since patients in the early active stage of the disease are more likely to respond to anti-inflammatory and immunosuppressive therapies, whereas patients in the late fibrotic stage require different therapeutic approaches, including rehabilitative surgery. METHODS: We reviewed cases of TED investigated with CT and Magnetic Resonance Imaging (MRI) in our department. We assessed the findings of imaging studies and their role in the clinical investigation of patients with TED as well as in the differential diagnosis from other disorders. RESULTS: Imaging has a significant role in the investigation of TED, however a consensus on the use of different imaging modalities in the course of disease has yet to be reached. Nevertheless, imaging and specifically CT and MRI can have a vital role in the initial diagnosis of clinically atypical presentation of TED, in surgical planning, as well as in the differential diagnosis from other orbital disorders. CONCLUSION: In this review, we attempt to present current trends in imaging investigation of TED. Rather than focusing on the findings of each imaging modality separately, we present the two main imaging modalities focusing on CT and MRI, in the context of pathogenic stages of the disease.

Prediction of a multiple sclerosis diagnosis in patients with clinically isolated syndrome using the 2016 MAGNIMS and 2010 McDonald criteria: a retrospective study.

BACKGROUND: In 2016, the Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS) network proposed modifications to the MRI criteria to define dissemination in space (DIS) and time (DIT) for the diagnosis of multiple sclerosis in patients with clinically isolated syndrome (CIS). Changes to the DIS definition included removal of the distinction between symptomatic and asymptomatic lesions, increasing the number of lesions needed to define periventricular involvement to three, combining cortical and juxtacortical lesions, and inclusion of optic nerve evaluation. For DIT, removal of the distinction between symptomatic and asymptomatic lesions was suggested. We compared the performance of the 2010 McDonald and 2016 MAGNIMS criteria for multiple sclerosis diagnosis in a large multicentre cohort of patients with CIS to provide evidence to guide revisions of multiple sclerosis diagnostic criteria. METHODS: Brain and spinal cord MRI and optic nerve assessments from patients with typical CIS suggestive of multiple sclerosis done less than 3 months from clinical onset in eight European multiple sclerosis centres were included in this retrospective study. Eligible patients were 16-60 years, and had a first CIS suggestive of CNS demyelination and typical of relapsing-remitting multiple sclerosis, a complete neurological examination, a baseline brain and spinal cord MRI scan obtained less than 3 months from clinical onset, and a follow-up brain scan obtained less than 12 months from CIS onset. We recorded occurrence of a second clinical attack (clinically definite multiple sclerosis) at months 36 and 60. We evaluated MRI criteria performance for DIS, DIT, and DIS plus DIT with a time-dependent receiver operating characteristic curve analysis. FINDINGS: Between June 16, 1995, and Jan 27, 2017, 571 patients with CIS were screened, of whom 368 met all study inclusion criteria. At the last evaluation (median 50·0 months [IQR 27·0-78·4]), 189 (51%) of 368 patients developed clinically definite multiple sclerosis. At 36 months, the two DIS criteria showed high sensitivity (2010 McDonald 0·91 [95% CI 0·85-0·94] and 2016 MAGNIMS 0·93 [0·88-0·96]), similar specificity (0·33 [0·25-0·42] and 0·32 [0·24-0·41]), and similar area under the curve values (AUC; 0·62 [0·57-0·67] and 0·63 [0·58-0·67]). Performance was not affected by inclusion of symptomatic lesions (sensitivity 0·92 [0·87-0·96], specificity 0·31 [0·23-0·40], AUC 0·62 [0·57-0·66]) or cortical lesions (sensitivity 0·92 [0·87-0·95], specificity 0·32 [0·24-0·41], AUC 0·62 [0·57-0·67]). Requirement of three periventricular lesions resulted in slightly lower sensitivity (0·85 [0·78-0·90], slightly higher specificity (0·40 [0·32-0·50], and similar AUC (0·63 [0·57-0·68]). Inclusion of optic nerve evaluation resulted in similar sensitivity (0·92 [0·87-0·96]), and slightly lower specificity (0·26 [0·18-0·34]) and AUC (0·59 [0·55-0·64]). AUC values were also similar for DIT (2010 McDonald 0·61 [0·55-0·67] and 2016 MAGNIMS 0·61 [0·55-0·66]) and DIS plus DIT (0·62 [0·56-0·67] and 0·64 [0·58-0·69]). INTERPRETATION: The 2016 MAGNIMS criteria showed similar accuracy to the 2010 McDonald criteria in predicting the development of clinically definite multiple sclerosis. Inclusion of symptomatic lesions is expected to simplify the clinical use of MRI criteria without reducing accuracy, and our findings suggest that needing three lesions to define periventricular involvement might slightly increase specificity, suggesting that these two factors could be considered during further revisions of multiple sclerosis diagnostic criteria. FUNDING: UK MS Society, National Institute for Health Research University College London Hospitals Biomedical Research Centre, Dutch MS Research Foundation.

Orbital melanoma masquerading as a "Galloping haemangioma".

We describe a 32-year-old pregnant woman who was referred to our clinic after 6 weeks of observation elsewhere with a rapidly expanding orbital mass, proptosed globe and slowly decreasing of vision in her left eye. To our examination the patient presented with congested optic disc fine macular striae and some slight choroidal elevation without any retinal pigmentation. An MRI scan without contrast was performed, suggesting the signal charactheristics of an orbital mass consistent with a cellular lesion such as a cavernous hemangioma or a solitary fibrous tumour. Despite the benign-looking imaging, the fast-growing pattern of the lesion suggested a more sinister picture. A fine needle aspiration of the orbital mass was carried out, revealing the presence of an amelanotic melanoma. This case highlights the importance of considering the presence of a melanoma when there is a clear history of a rapid lesion progression.

Periventricular lesions and MS diagnostic criteria in young adults with typical clinically isolated syndromes.

In patients who present with a clinically isolated syndrome (CIS), whose features are suggestive of multiple sclerosis (MS), fulfilling McDonald 2010 magnetic resonance imaging (MRI) criteria for dissemination in space (DIS) and dissemination in time (DIT) enables a diagnosis of MS. While ⩾1 periventricular lesion is included in the 2010 DIS criteria, earlier McDonald criteria required ⩾3 periventricular lesions to confirm DIS and recent Magnetic Resonance Imaging in Multiple Sclerosis (MAGNIMS)-recommended DIS criteria also require ⩾3 lesions. We investigated the effect of varying the required number of periventricular lesions and found that the best combination of specificity and sensitivity for clinically definite MS was seen for ⩾1 periventricular lesion using both the McDonald 2010 and MAGNIMS 2016 criteria.

Should the symptomatic region be included in dissemination in space in MRI criteria for MS?

OBJECTIVES: To investigate whether inclusion of lesions in the symptomatic region influences the performance of dissemination in space (DIS) criteria for a diagnosis of clinically definite multiple sclerosis (CDMS) in patients with a clinically isolated syndrome (CIS). METHODS: We studied 30 patients with CIS with brainstem/cerebellar and spinal cord syndromes who had MRI scans at the time of CIS and were followed up for the development of CDMS. We retrospectively applied the McDonald 2010 DIS criteria (excluding all lesions in the symptomatic region) to baseline MRI scans and 2 modified DIS criteria: (1) the inclusion of asymptomatic lesions in the symptomatic region in DIS, and (2) the inclusion of any lesion in the symptomatic region in DIS. The performance of the McDonald 2010 DIS criteria and the 2 modified criteria for the development of CDMS was compared. RESULTS: The sensitivity, specificity, and accuracy of the DIS criteria was, respectively, 73%, 73%, and 73% for the McDonald 2010 criteria, 80%, 73%, and 77% when asymptomatic lesions in the symptomatic region were included, and 87%, 73%, and 80% when any lesion in the symptomatic region was included in DIS. CONCLUSIONS: Including lesions in the symptomatic region in DIS increases the sensitivity of MRI criteria for diagnosing multiple sclerosis without compromising specificity. These findings may help inform future revisions of the diagnostic criteria for multiple sclerosis. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with CIS, including lesions in the symptomatic region as part of the criteria for DIS does not significantly increase the accuracy for predicting the development of CDMS. The study lacks the precision to detect an important change in accuracy.

Evaluation of the stability of the stereotactic Leksell Frame G in Gamma Knife radiosurgery.

The purpose of this study was to evaluate the stability of the Leksell Frame G in Gamma Knife radiosurgery (GKR). Forty patients undergoing GKR underwent pretreatment stereotactic MRI for GKR planning and stereotactic CT immediately after GKR. The stereotactic coordinates of four anatomical landmarks (cochlear apertures and the summits of the anterior post of the superior semicircular canals, bilaterally) were measured by two evaluators on two separate occasions in the pre-treatment MRI and post-treatment CT scans and the absolute distance between the observations is reported. The measurement method was validated with an indepen-dent group of patients who underwent both stereotactic MRI and CT imaging before treatment (negative controls; n: 5). Patients undergoing GKR for arteriovenous malformations (AVM) also underwent digital subtraction angiography (DSA), which could result in extra stresses on the frame. The distance between landmark local-ization in the scans for the negative control group (0.63 mm; 95% CI: 0.57-0.70; SD: 0.29) represents the overall consistency of the evaluation method and provides an estimate of the minimum displacement that could be detected by the study. Two patients in the study group had the fiducial indicator box accidentally misplaced at post-treatment CT scanning. This simulated the scenario of a frame displacement, and these cases were used as positive controls to demonstrate that the evaluation method is capable of detecting a discrepancy between the MRI and CT scans, if there was one. The mean distance between the location of the landmarks in the pretreatment MRI and post-treatment CT scans for the study group was 0.71 mm (95% CI: 0.68-0.74; SD:0.32), which was not statistically different from the over-all uncertainty of the evaluation method observed in the negative control group (p = 0.06). The subgroup of patients with AVM (n: 9), who also underwent DSA, showed a statistically significant difference between the location of the landmarks compared to subjects with no additional imaging: 0.78 mm (95% CI: 0.72-0.84) vs. 0.69 mm (95% CI: 0.66-0.72), p = 0.016. This is however a minimal differ-ence (0.1 mm) and the mean difference in landmark location for each AVM patient remained submillimeter. This study demonstrates submillimeter stability of the Leksell Frame G in GKR throughout the treatment procedure.

Longitudinal evidence for anterograde trans-synaptic degeneration after optic neuritis.

In multiple sclerosis, microstructural damage of normal-appearing brain tissue is an important feature of its pathology. Understanding these mechanisms is vital to help develop neuroprotective strategies. The visual pathway is a key model to study mechanisms of damage and recovery in demyelination. Anterograde trans-synaptic degeneration across the lateral geniculate nuclei has been suggested as a mechanism of tissue damage to explain optic radiation abnormalities seen in association with demyelinating disease and optic neuritis, although evidence for this has relied solely on cross-sectional studies. We therefore aimed to assess: (i) longitudinal changes in the diffusion properties of optic radiations after optic neuritis suggesting trans-synaptic degeneration; (ii) the predictive value of early optic nerve magnetic resonance imaging measures for late optic radiations changes; and (iii) the impact on visual outcome of both optic nerve and brain post-optic neuritis changes. Twenty-eight consecutive patients with acute optic neuritis and eight healthy controls were assessed visually (logMAR, colour vision, and Sloan 1.25%, 5%, 25%) and by magnetic resonance imaging, at baseline, 3, 6, and 12 months. Magnetic resonance imaging sequences performed (and metrics obtained) were: (i) optic nerve fluid-attenuated inversion-recovery (optic nerve cross-sectional area); (ii) optic nerve proton density fast spin-echo (optic nerve proton density-lesion length); (iii) optic nerve post-gadolinium T1-weighted (Gd-enhanced lesion length); and (iv) brain diffusion-weighted imaging (to derive optic radiation fractional anisotropy, radial diffusivity, and axial diffusivity). Mixed-effects and multivariate regression models were performed, adjusting for age, gender, and optic radiation lesion load. These identified changes over time and associations between early optic nerve measures and 1-year global optic radiation/clinical measures. The fractional anisotropy in patients' optic radiations decreased (P = 0.018) and radial diffusivity increased (P = 0.002) over 1 year following optic neuritis, whereas optic radiation measures were unchanged in controls. Also, smaller cross-sectional areas of affected optic nerves at 3 months post-optic neuritis predicted lower fractional anisotropy and higher radial diffusivity at 1 year (P = 0.007) in the optic radiations, whereas none of the inflammatory measures of the optic nerve predicted changes in optic radiations. Finally, greater Gd-enhanced lesion length at baseline and greater optic nerve proton density-lesion length at 1 year were associated with worse visual function at 1 year (P = 0.034 for both). Neither the cross-sectional area of the affected optic nerve after optic neuritis nor the damage in optic radiations was associated with 1-year visual outcome. Our longitudinal study shows that, after optic neuritis, there is progressive damage to the optic radiations, greater in patients with early residual optic nerve atrophy, even after adjusting for optic radiation lesions. These findings provide evidence for trans-synaptic degeneration.

Grey matter involvement by focal cervical spinal cord lesions is associated with progressive multiple sclerosis.

BACKGROUND: The in vivo relationship of spinal cord lesion features with clinical course and function in multiple sclerosis (MS) is poorly defined. OBJECTIVE: The objective of this paper is to investigate the associations of spinal cord lesion features on MRI with MS subgroup and disability. METHODS: We recruited 120 people: 25 clinically isolated syndrome, 35 relapsing-remitting (RR), 30 secondary progressive (SP), and 30 primary progressive (PP) MS. Disability was measured using the Expanded Disability Status Scale. We performed 3T axial cervical cord MRI, using 3D-fast-field-echo and phase-sensitive-inversion-recovery sequences. Both focal lesions and diffuse abnormalities were recorded. Focal lesions were classified according to the number of white matter (WM) columns involved and whether they extended to grey matter (GM). RESULTS: The proportion of patients with focal lesions involving at least two WM columns and extending to GM was higher in SPMS than in RRMS (p = 0.03) and PPMS (p = 0.015). Diffuse abnormalities were more common in both PPMS and SPMS, compared with RRMS (OR 6.1 (p = 0.002) and 5.7 (p = 0.003), respectively). The number of lesions per patient involving both the lateral column and extending to GM was independently associated with disability (p < 0.001). CONCLUSIONS: More extensive focal cord lesions, extension of lesions to GM, and diffuse abnormalities are associated with progressive MS and disability.

Tablets or scalpel: Pituitary hyperplasia due to primary hypothyroidism.

We describe a patient with pituitary hyperplasia due to primary hypothyroidism. Pituitary hyperplasia and pituitary masses cannot be reliably differentiated on imaging alone, despite significant improvement in imaging quality in recent years.

Early factors associated with axonal loss after optic neuritis.

OBJECTIVE: Acute optic neuritis due to an inflammatory demyelinating lesion of the optic nerve is often seen in association with multiple sclerosis. Although functional recovery usually follows the acute episode of visual loss, persistent visual deficits are common and are probably due to axonal loss. The mechanisms of axonal loss and early features that predict it are not well defined. We investigated clinical, electrophysiological, and imaging measures at presentation and after 3 months as potential markers of axonal loss following optic neuritis. METHODS: We followed 21 patients after their first attack of acute unilateral optic neuritis for up to 18 months. Axonal loss was inferred from optical coherence tomography measures of retinal nerve fiber layer (RNFL) thickness at least 6 months following the episode. Visual function, visual evoked potential, and optic nerve magnetic resonance imaging measures obtained during the acute episode and 3 months later were investigated for their association with later axonal loss. RESULTS: After multivariate analysis, prolonged visual evoked potential latency and impaired color vision, at baseline and after 3 months, were significantly and independently associated with RNFL thinning. Low-contrast acuity measures exhibited significant univariate associations with RNFL thinning. INTERPRETATION: The association of RNFL loss with a prolonged visual evoked potential (VEP) latency suggests that acute and persistent demyelination is associated with increased vulnerability of axons. VEP latency and visual function tests that capture optic nerve function, such as color and contrast, may help identify subjects with a higher risk for axonal loss who are thus more suitable for experimental neuroprotection trials.

Neuroplasticity predicts outcome of optic neuritis independent of tissue damage.

OBJECTIVES: To determine whether lateral occipital complex (LOC) activation with functional magnetic resonance imaging (fMRI) predicts visual outcome after clinically isolated optic neuritis (ON). To investigate the reasons behind good recovery following ON, despite residual optic nerve demyelination and neuroaxonal damage. METHODS: Patients with acute ON and healthy volunteers were studied longitudinally over 12 months. Structural MRI, visual evoked potentials (VEPs), and optical coherence tomography (OCT) were used to quantify acute inflammation, demyelination, conduction block, and later to estimate remyelination and neuroaxonal loss over the entire visual pathway. The role of neuroplasticity was investigated using fMRI. Multivariable linear regression analysis was used to study associations between vision, structure, and function. RESULTS: Greater baseline fMRI responses in the LOCs were associated with better visual outcome at 12 months. This was evident on stimulation of either eye (p = 0.007 affected; p = 0.020 fellow eye), and was independent of measures of demyelination and neuroaxonal loss. A negative fMRI response in the LOCs at baseline was associated with a relatively worse visual outcome. No acute electrophysiological or structural measures, in the anterior or posterior visual pathways, were associated with visual outcome. INTERPRETATION: Early neuroplasticity in higher visual areas appears to be an important determinant of recovery from ON, independent of tissue damage in the anterior or posterior visual pathway, including neuroaxonal loss (as measured by MRI, VEP, and OCT) and demyelination (as measured by VEP).

Dissecting structure-function interactions in acute optic neuritis to investigate neuroplasticity.

Structural MRI, electrophysiology, and functional MRI (fMRI) elucidate different aspects of damage and repair in demyelinating diseases. We combined them to investigate why patients with optic neuritis (ON) exhibit a wide variation in severity of acute visual loss, with the following objectives: (1) To determine how structural and electrophysiological changes in the anterior and posterior visual pathways contribute to acute visual loss. (2) To combine these data with fMRI, to investigate whether cortical activity modulates visual acuity. The visual system of 28 patients with acute unilateral ON was assessed. Linear regression modeling was used to identify parameters associated with acute visual loss, and to determine whether fMRI activity was associated with vision, after accounting for structural and electrophysiological predictors, age, and gender. Optic nerve lesion length and visual evoked potential (VEP) amplitude were associated with visual loss. Bilateral activation in the extra-striate occipital cortex correlated directly with vision, after adjusting for optic nerve lesion length, VEP amplitude, and demographic characteristics. These data suggest that acute visual loss is associated with the extent of inflammation and conduction block in the optic nerve, but not with pathology in the optic radiations or occipital cortex. The association of better vision with greater fMRI responses, after accounting for factors which reduce afferent input, suggests a role for adaptive neuroplasticity within the association cortex of the dorsal stream of higher visual processing. Longitudinal studies will clarify whether different extra-striate cortical regions play a role in adaptive plasticity in the acute and chronic stages of injury.