Deep gray matter changes in relapsing-remitting multiple sclerosis detected by multi-parametric, high-resolution magnetic resonance imaging (MRI).

OBJECTIVES: To investigate a variety of magnetic resonance imaging (MRI) quantitative metrics, which reflect different aspects of microstructural damage in deep gray matter (dGM) regions and white matter T2 lesions in patients with relapsing-remitting multiple sclerosis (RRMS), and to determine the level of pathological interconnection between these two entities as well as their association with clinical disability. METHODS: We recruited thirty RRMS patients along with thirty age-matched healthy controls (HCs). Both groups were scanned at 3 T MRI using 3D high-resolution T1-, T2-, and T2*-weighted, magnetization transfer (MT)-prepared gradient echo for MT ratio (MTR) mapping, and eight repeats of T1-weighted images acquired at different inversion times to create T1 maps. dGM structures were segmented from T1-weighted images using FreeSurfer, WM-T2 lesions were extracted from T2-weighted images, and iron maps were calculated from the phase part of the T2*-weighted sequence. Extracted dGM MRI indices were compared between both groups. In the RRMS group, dGM MRI indices were correlated with those of WM-T2 lesions, expanded disability status scale, and disease duration. RESULTS: dGM volumetric metrics of RRMS patients were significantly (p < 0.01) smaller than those of HCs and showed a significant moderate association with lesions' load (p < 0.05) and lesions' iron concentration (p < 0.01). dGM MTRs of RRMS patients were significantly (p < 0.01) smaller than those of HCs and showed a significant (p < 0.01) moderate correlation with lesion T1 times. While T1 changes in some dGM regions of RRMS patients associated weakly with those of T2 lesions, dGM iron concentration did not show any association with any of lesions' metrics. Furthermore, lesions' MTR changes did not show any association with any dGM metrics. Most dGM metrics did not show any correlation with disease severity. Contrarily, most lesions' metrics showed weak association with disease severity. CONCLUSIONS: dGM changes occur in a non-uniform pattern and, almost, do not link directly to MS disease severity. Contrarily, most WM-T2 lesions' metrics tend to correlate with MS disease severity better than those of dGM. KEY POINTS: • Deep gray matter (dGM) structures are very much involved in the MS disease process and quite substantial neurodegeneration is undergone during the relapsing-remitting phase of the MS disease. • Deep gray matter (dGM) quantitative changes occur in a non-uniform and non-linked pattern and, except for CN's iron deposition, do not directly associate with the MS disease severity. • Most white matter T2 lesions' metrics tend to correlate with MS disease severity better than those of dGM structures.

A regional consensus recommendation on brain atrophy as an outcome measure in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune disease characterized by inflammatory and neurodegenerative processes leading to irreversible neurological impairment. Brain atrophy occurs early in the course of the disease at a rate greater than the general population. Brain volume loss (BVL) is associated with disability progression and cognitive impairment in patients with MS; hence its value as a potential target in monitoring and treating MS is discussed. METHODS: A group of MS neurologists and neuro-radiologists reviewed the current literature on brain atrophy and discussed the challenges in assessing and implementing brain atrophy measurements in clinical practice. The panel used a voting system to reach a consensus and the votes were counted for the proposed set of questions for cognitive and brain atrophy assessments. RESULTS: The panel of experts was able to identify recent studies, which demonstrated the correlation between BVL and future worsening of disability and cognition. The current evidence revealed that reduction of BVL could be achieved with different disease-modifying therapies (DMTs). BVL provided a better treatment and monitoring strategy when it is combined to the composite measures of "no evidence of disease activity" (NEDA). The panel recommended a set of cognitive assessment tools and MRI methods and software applications that may help in capturing and measuring the underlying MS pathology with high degree of specificity. CONCLUSION: BVL was considered to be a useful measurement to longitudinally assess disease progression and cognitive function in patients with MS. Brain atrophy measurement was recommended to be incorporated into the concept of NEDA. Consequently, a consensus recommendation was reached in anticipation for implementation of the use of cognitive assessment and brain atrophy measurements on a regional level.

Cortical and Subcortical Morphometric and Iron Changes in Relapsing-Remitting Multiple Sclerosis and Their Association with White Matter T2 Lesion Load : A 3-Tesla Magnetic Resonance Imaging Study.

INTRODUCTION: This study was carried out to investigate the global and regional morphometric and iron changes in grey matter (GM) of multiple sclerosis (MS) patients and link them to the white matter (WM) lesions in a multimodal magnetic resonance imaging approach. MATERIAL AND METHODS: The study involved 30 relapsing-remitting MS (RRMS) patients along with 30 age-matched healthy controls (HC) who were scanned on a 3T Siemens Trio system. The scanning protocol included a 3D, high resolution T1, T2, and T2*-weighted sequences. The T1-w images were used in FreeSurfer for cortical reconstruction and volumetric segmentation, while T2-w images were used to extract the WM T2 lesions; however, iron and magnetic susceptibility were calculated from the phase data of the T2*-w sequence. Surface-based analyses were performed in FreeSurfer to investigate the regional cortical morphometric changes and their correlations with the expanded disability status scale (EDSS), WM T2 lesions load, cortical iron deposition and magnetic susceptibility. RESULTS: Significant differences were detected between the RRMS patients and HC for all cortical and subcortical morphometric changes. The EDSS and T2 lesion load showed weak to moderate correlation with the reduced cortical morphometric measurements, increased cortical magnetic susceptibility and iron concentration. All deep grey matter (dGM) volumes showed a significant strong positive correlation with the cortical surface area and volume in RRMS patients and HC. CONCLUSIONS: Grey matter is very much involved in the RRMS and cortical morphometric changes occur in a non-uniform pattern and are very likely to be associated with cortical iron deposition and magnetic susceptibility, dGM atrophy, WM T2 lesion load, and disability.

Improving the likelihood of neurology patients being examined using patient feedback.

We aimed to establish whether recall of elements of the neurological examination can be improved by use of a simple patient assessment score. In a previous study we demonstrated that in-patients referred to neurology at two United Kingdom (UK) hospitals were not fully examined prior to referral; we therefore designed a larger quality improvement report with 80% power to detect a 10% increase in tendon hammer or ophthalmoscope use following an educational intervention. In-patients referred to neurology over a four month period (in hospitals in the UK (10), Jordan (1), Sweden (2), and the United Arab Emirates (1)) were asked whether they recalled being examined with a tendon hammer (T), ophthalmoscope (O), and stethoscope (S) since admission. The results were disseminated to local medical teams using various techniques (including Grand Round presentations, email, posters, discounted equipment). Data were then collected for a further four month period post-intervention. Pre-intervention and post-intervention data were available for 11 centres with 407 & 391 patients in each arm respectively. Median age of patients was 51 (range 13-100) and 49 (range 16-95) years respectively, with 44.72% and 44.76% being male in each group. 264 patients (64.86%) recalled being examined with a tendon hammer in the pre-intervention arm, which significantly improved to 298 (76.21%) (p<0.001). Only 119 patients (29.24%) recollected examination with an ophthalmoscope pre-intervention, which significantly improved to 149 (38.11%)(p=0.009). The majority of patients (321 (78.87%)) pre-intervention recalled examination with a stethoscope, which significantly improved to 330 (84.4%) to a lesser extent (p=0.045). Results indicate that most patients are not fully examined prior to neurology referral yet a simple assessment score and educational intervention can improve recall of elements of the neurological examination and thus the likelihood of patients being examined neurologically. This is the largest and - to our knowledge - only study to assess this issue. This has implications for national neurological educators.

Rapidly progressive bilateral ophthalmoplegia and enlarging sellar mass caused by amelanotic melanoma.

A 63-year-old woman with diplopia and bilateral ptosis underwent brain MRI that showed a pituitary mass with signal characteristics suggestive of adenoma. Within one week she had developed nearly complete bilateral ophthalmoplegia. A repeat MRI showed extension of the mass into both cavernous sinuses. Hypophysectomy disclosed an amelanotic melanoma. Extensive search for a primary source was unsuccessful. Despite local radiation treatment, the tumor continued to grow and the patient became blind and died within several months of diagnosis. There are seven reported cases of melanoma arising primarily in the sella turcica. Two cases of metastatic melanoma to the cavernous sinuses have been reported. Amelanotic melanoma has not been reported as a cause of cavernous sinus syndrome.

Optimizing the use of electrophysiology in the diagnosis of chronic inflammatory demyelinating polyneuropathy: a study of 20 cases.

Current electrophysiologic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP) are highly specific but poorly sensitive. The required extensiveness and best practical way of performing nerve conduction studies to achieve optimal sensitivity remain unknown. We here initially retrospectively analyzed the motor nerve conduction study results of 20 consecutive patients with a clinical diagnosis of CIDP (four performed prior to, and 16 after, treatment initiation) to assess the sensitivity of six published sets of criteria (Nicolas et al., 2002; Thaisetthawatkul et al., 2002; Ad Hoc Subcommittee of the American Academy of Neurology AIDS Taskforce, 1991; Magda et al., 2003; Hughes et al., 2001; Saperstein et al., 2001), as well as four combinations (Nicolas et al., 2002; Ad Hoc Subcommittee of the American Academy of Neurology AIDS Taskforce, 1991; Hughes et al., 2001; Saperstein et al., 2001, each individually combined with Thaisetthawatkul et al., 2002). Sensitivity was highest for the combination of Nicolas et al. (2002) and Thaisetthawatkul et al. (2002) (100%). We then determined the sensitivity of this combined criteria, using five different, hypothetical, nerve conduction study protocols, applied retrospectively to the neurophysiologic data of our 20 patients (exclusive upper limb studies with proximal stimulations; exclusive lower limb studies; full forearm and foreleg studies without proximal stimulations; right-sided studies with proximal stimulations; and left-sided studies with proximal stimulations). The findings showed that exhaustive upper limb or, alternatively, four-limb forearm and foreleg testing would have proved considerably more sensitive than unilateral or lower limb studies to achieve an electrophysiologic diagnosis of CIDP.