No abstract

Atypical imaging features of multiple sclerosis lesions include size >2 cm, mass effect, oedema and/or ring enhancement. This constellation is often referred to as ‘tumefactive multiple sclerosis’. Previous series emphasize their unifocal and clinically isolated nature, however, evolution of these lesions is not well defined. Biopsy may be required for diagnosis. We describe clinical and radiographic features in 168 patients with biopsy confirmed CNS inflammatory demyelinating disease (IDD). Lesions were analysed on pre- and post-biopsy magnetic resonance imaging (MRI) for location, size, mass effect/oedema, enhancement, multifocality and fulfilment of Barkhof criteria. Clinical data were correlated to MRI. Female to male ratio was 1.2 : 1, median age at onset, 37 years, duration between symptom onset and biopsy, 7.1 weeks and total disease duration, 3.9 years. Clinical course prior to biopsy was a first neurological event in 61%, relapsing–remitting in 29% and progressive in 4%. Presentations were typically polysymptomatic, with motor, cognitive and sensory symptoms predominating. Aphasia, agnosia, seizures and visual field defects were observed. At follow-up, 70% developed definite multiple sclerosis, and 14% had an isolated demyelinating syndrome. Median time to second attack was 4.8 years, and median EDSS at follow-up was 3.0. Multiple lesions were present in 70% on pre-biopsy MRI, and in 83% by last MRI, with Barkhof criteria fulfilled in 46% prior to biopsy and 55% by follow-up. Only 17% of cases remained unifocal. Median largest lesion size on T2-weighted images was 4 cm (range 0.5–12), with a discernible size of 2.1 cm (range 0.5–7.5). Biopsied lesions demonstrated mass effect in 45% and oedema in 77%. A strong association was found between lesion size, and presence of mass effect and/or oedema (P < 0.001). Ring enhancement was frequent. Most tumefactive features did not correlate with gender, course or diagnosis. Although lesion size >5 cm was associated with a slightly higher EDSS at last follow-up, long-term prognosis in patients with disease duration >10 years was better (EDSS 1.5) compared with a population-based multiple sclerosis cohort matched for disease duration (EDSS 3.5; P < 0.001). Given the retrospective nature of the study, the precise reason for biopsy could not always be determined. This study underscores the diagnostically challenging nature of CNS IDDs that present with atypical clinical or radiographic features. Most have multifocal disease at onset, and develop RRMS by follow-up. Although increased awareness of this broad spectrum may obviate need for biopsy in many circumstances, an important role for diagnostic brain biopsy may be required in some cases.

Background: The authors previously proposed diagnostic criteria for neuromyelitis optica (NMO) that facilitate its distinction from prototypic multiple sclerosis (MS). However, some patients with otherwise typical NMO have additional symptoms not attributable to optic nerve or spinal cord inflammation or have MS-like brain MRI lesions. Furthermore, some patients are misclassified as NMO by the authors' earlier proposed criteria despite having a subsequent course indistinguishable from prototypic MS. A serum autoantibody marker, NMO-IgG, is highly specific for NMO. The authors propose revised NMO diagnostic criteria that incorporate NMO-IgG status. Methods: Using final clinical diagnosis (NMO or MS) as the reference standard, the authors calculated sensitivity and specificity for each criterion and various combinations using a sample of 96 patients with NMO and 33 with MS. The authors used likelihood ratios and logistic regression analysis to develop the most practical and informative diagnostic model. Results: Fourteen patients with NMO (14.6%) had extra-optic-spinal CNS symptoms. NMO-IgG seropositivity was 76% sensitive and 94% specific for NMO. The best diagnostic combination was 99% sensitive and 90% specific for NMO and consisted of at least two of three elements: longitudinally extensive cord lesion, onset brain MRI nondiagnostic for MS, or NMO-IgG seropositivity. Conclusions: The authors propose revised diagnostic criteria for definite neuromyelitis optica (NMO) that require optic neuritis, myelitis, and at least two of three supportive criteria: MRI evidence of a contiguous spinal cord lesion 3 or more segments in length, onset brain MRI nondiagnostic for multiple sclerosis, or NMO-IgG seropositivity. CNS involvement beyond the optic nerves and spinal cord is compatible with NMO.

Ring-enhancing lesions seen on MR images can occur with a variety of etiologies. Some ring-enhancing lesions have hypointense rims peripherally on T2-weighted MR images. In this study, we examined whether T2 hypointense rims were associated with specific pathologies. A search for ring-enhancing lesions on MR images obtained from 1996 to 2004 was performed, and revealed 221 patients with MRI findings of ring enhancement. The pattern of T2 hypointensity (arc or rim) corresponding with ring enhancement was recorded. In addition, we analyzed other imaging characteristics, including signal on diffusion-weighted images, central homogeneity on T2 and multiplicity of lesions. We then reviewed clinical data on the patients to ascertain the diagnosis for each examination. The most common associated pathologies in our study were gliomas (40%), metastases (30%), abscesses (8%) and multiple sclerosis (MS; 6%). Hypointense borders on T2-weighted images were present in 67% of lesions in the form of a rim in 40% and an arc in 60%. Abscesses had the highest percentage of hypointense rims. Metastases and gliomas more commonly had arcs, and MS lesions were divided between rims and arcs. Abscesses and MS lesions were more commonly homogeneous centrally, compared to gliomas and metastases. Additionally, abscesses were more often bright on diffusion imaging than the other pathologies. As expected, abscesses and MS lesions were usually multiple, whereas metastases were typically multiple in approximately 50% of the patients; gliomas were generally solitary. Trends in T2 hypointensity may aid in distinguishing among etiologies of ring-enhancing lesions, although there is overlap between the MR appearance of these various pathologies.

Pharmacotherapeutic options for multiple sclerosis (MS)-related fatigue are limited. Thirty patients were randomly assigned to aspirin (ASA) 1,300 mg/day or placebo in a double-blind crossover study. Results favored ASA for the main clinical outcomes: Modified Fatigue Impact Scale scores (p = 0.043) and treatment preference (p = 0.012). There were no significant adverse effects. The results warrant further study and support a role for ASA-influenced mechanisms, perhaps immunologic, in the generation of MS-related chronic fatigue.

Leukoencephalopathy with neuroaxonal spheroids occurs sporadically, in adults, and mimics cerebral-type MS or other leukodystrophies. Brain biopsy may be diagnostic in life; however, no treatment is known to be effective. Pathologic diagnosis is important to avoid potentially toxic therapies aimed at CNS inflammatory diseases such as MS.

The present review will focus on the current knowledge of the pathology of primary progressive multiple sclerosis lesions. Multiple sclerosis (MS) is an inflammatory demyelinating disease with a broad clinical variability. The main disease courses are relapsing-remitting, secondary progressive and primary progressive MS. Pathological studies examining the specific underlying pathology of a defined clinical subtype are rare. Here, we focus on the pathological characteristics of the MS lesions and summarize the current findings of the pathology of primary progressive MS with respect to inflammation, oligodendrocyte myelin pathology, axon destruction and immunopathology of the lesions.

Background and Purpose To determine whether a novel double inversion recovery MRI technique has the potential to increase the specificity of diagnostic criteria distinguishing MS from non-MS white matter lesions. Materials and Methods This is a cross-sectional observational study. MRI data were acquired between 2011 and 2016. A novel double-inversion-recovery sequence that suppresses CSF and GM signal was used (GM-DIR). We compared WM lesions in a group of patients with multiple sclerosis and in a second group of positive controls (PC) with white matter lesions that did not have a diagnosis of MS. The presence of a rim on GM-DIR MRI sequence was combined with the 2001 and 2010 McDonald DIS criteria. Multiple MRI markers including lesion location, size and presence of rim were compared between groups as well as quantitative measure of lesion T1-hypointensity. Results MRI scans from 107 patients with RRMS (median age 32) and 36 positive control (PC, median age 39) subjects were analyzed. No significant differences were present in age and sex. In MS, 1120/3211 lesions (35%) had a rim on GM-DIR; the PC group had only 9/893 rim lesions (1%). Rims were associated with a decrease in lesion T1-ratio. Using the 2010 MRI criteria plus the presence of rims on GM-DIR, we achieved 78% and 97% specificity in subjects with ≥ 1 and ≥ 2 rim-lesions respectively. Conclusion The addition of a novel GM-DIR technique enhanced specificity for diagnosing MS compared to established MRI criteria.