Concomitant granule cell neuronopathy in patients with natalizumab-associated PML

Granule cell neuronopathy (GCN) is a rare JC virus infection of the cerebellar granule cell neurons in immunocompromised patients. On brain imaging, GCN is characterized by cerebellar atrophy which can be accompanied by infratentorial white matter lesions. The objective of this study is to investigate the prevalence of MRI findings suggestive of GCN in a large natalizumab-associated progressive multifocal leukoencephalopathy (PML) cohort. MRI scans from before, at the time of, and during follow-up after diagnosis of PML in 44 natalizumab-treated MS patients, and a control group of 25 natalizumab-treated non-PML MS patients were retrospectively reviewed for imaging findings suggestive of GCN. To assess and quantify the degree of cerebellar atrophy, we used a 4 grade rating scale. Three patients in the PML group showed imaging findings suggestive of GCN and none in the control group. In two of these PML patients, cerebellar atrophy progressed from grade 0 at the time of diagnosis of isolated supratentorial PML to grade 1 and 2 after 2.5 and 3 months, respectively, in the absence of infratentorial white mater lesions. The third patient had grade 1 cerebellar atrophy before diagnosis of infra- and supratentorial PML, and showed progression of cerebellar atrophy to grade 2 in the 3 months following PML diagnosis. None of the other eight patients with infratentorial PML lesions developed cerebellar atrophy suggestive of GCN. Three cases with imaging findings suggestive of GCN were detected among 44 natalizumab-associated PML patients. GCN may, therefore, be more common than previously considered in natalizumab-associated PML patients

Retinal nerve fiber layer thickness in subgroups of multiple sclerosis, measured by optical coherence tomography and scanning laser polarimetry

Optical coherence tomography (OCT) and scanning laser polarimetry (GDx ECC) are non-invasive methods used to assess retinal nerve fiber layer (RNFL) thickness, which may be a reliable tool used to monitor axonal loss in multiple sclerosis (MS). The objectives of this study are (1) to compare OCT with the GDx ECC; (2) to assess and compare the RNFL thickness in subgroups of MS. Ophthalmologic examination and RNFL assessment by OCT and GDx were performed in 65 MS patients (26 relapsing-remitting (RRMS), ten secondary-progressive (SPMS), 29 primary-progressive (PPMS)). Twenty-eight patients (43%) had a history of optic neuritis (ON). Adjustments were made for age and disease duration. RNFL thickness was reduced in eyes with previous ON (p < 0.01). No differences were found between PPMS and relapse-onset MS. OCT and GDx ECC measurements were moderately correlated (rho = 0.73, p < 0.01). Visual field-mean deviation (MD) values correlated with OCT means (r = 0.44, p < 0.01) and GDx ECC TSNIT average (r = 0.41, p < 0.01). In patients without previous ON, EDSS correlated with MD (r = -0.36, p < 0.01), visual field-pattern standard deviation (PSD) (r = 0.30, p < 0.05), OCT means (r = -0.31-0.30, p < 0.05) and macular volume (r = -0.37, p < 0.01). For MSIS-29 physical impact score, significant correlations were found with MD (r = -0.48, p < 0.01) and PSD (r = 0.48, p < 0.01). Conclusions: No differences between PPMS and relapse-onset MS subgroups were found. RNFL thickness was reduced in eyes with previous ON. Although OCT and GDx ECC findings were moderately correlated and showed significant correlations with measures of visual function in patients without previous ON, EDSS correlated significantly with visual and OCT measures, but not with GDx ECC

Fatigue at time of CIS is an independent predictor of a subsequent diagnosis of multiple sclerosis

Objective Fatigue is a common, disabling symptom of multiple sclerosis ( MS), but little is known about fatigue in patients with clinically isolated syndrome ( CIS), often the presenting symptom of MS. We aimed to investigate the prevalence and severity of fatigue in patients with CIS, and its association with a diagnosis of clinically definite MS ( CDMS). Methods 127 patients were consecutively included in our ongoing prospective CIS study. At baseline, clinical, demographic, laboratory and MRI data were collected, and fatigue severity was assessed using Krupp's Fatigue Severity Scale ( FSS); fatigue was defined as FSS >= 5.0. Fatigue scores were compared with scores of 113 healthy controls and with scores from the literature. The association of fatigue with CDMS was calculated using Cox regression models. Results The mean FSS of patients with CIS was 4.3, similar to MS patients, and significantly higher than that of healthy individuals ( p<0.001). Fatigue prevalence in patients with CIS ( 46.5%) was significantly higher than in controls ( p<0.001). Fifty-two patients ( 40.9%) reached CDMS during follow-up. Fatigue was associated with a diagnosis of CDMS in univariate analysis ( HR 2.6, 95% CI 1.5 to 4.6) and in multivariate analysis correcting for sex, age, neuroanatomical localisation of CIS, 25-OH-vitamin D, anxiety, depression, MRI dissemination in space and gadolinium enhancement ( HR 4.5, 95% CI 1.9 to 10.6). Conclusions Already at the stage of CIS, fatigue is a very common symptom, with a severity similar to fatigue in MS patients. This fatigue seems unrelated to the type or severity of the attack. Importantly, we found that fatigue was an independent predictor of a subsequent diagnosis of MS

The role of disability and depression in cognitive functioning within 2 years after multiple sclerosis diagnosis

Objectives To investigate cognitive functioning shortly after multiple sclerosis (MS) diagnosis and to examine the relationship with disability, depression and anxiety. Methods Data were available for 101 recently diagnosed MS patients and 117 healthy controls. Neuropsychological and clinical assessment included Rao's Brief Repeatable Battery, Expanded Disability Status Scale (EDSS), and Hospital Anxiety and Depression scale (HADS). Results Patients had lower scores than controls on timed tasks (Paced Auditory Serial Addition Test (PASAT3, p-value adjusted for age, sex and education = 0.04; PASAT2, p = 0.001), Word List Generation Test (WLG, p = 0.04)). Scores on Symbol Digit Modalities Test (SDMT; p = 0.001), PASAT3 (p = 0.01) and PASAT2 (p = 3.0 had significantly lower scores on Selective Reminding Test (SRTC, p = 0.04), SDMT (p = 0.002), PASAT3 (p = 0.002), PASAT2 (p < 0.001) and WLG (p = 0.01) than controls from the general population. Patients with clinically borderline scores of depression scored lower on SDMT (49.5 versus 57.1, p = 0.06) and PASAT3 (39.8 versus 47.1, p = 0.03). However, after adjustment for EDSS and time since disease onset, these differences were not statistically significant. Conclusion Within two years after diagnosis, patients with MS had lower scores compared to healthy controls on timed tasks, suggesting cognitive slowing in patients with early MS. Cognitive impairment was associated with symptoms of depression, but this association could be explained by differences in disability

Is a fetal origin of the posterior cerebral artery a risk factor for TIA or ischemic stroke?

Background Fetal origin of the posterior cerebral artery (PCA) is not uncommon. Whether patients with this anomaly have a higher risk of ischemic stroke in the territory of the PCA is not known. The clinical benefit of screening for a fetal origin in patients with TIA or stroke in the territory of the PCA and an ipsilateral atherosclerotic carotid stenosis is not clear. This study assessed the frequency of a fetal origin of the PCA in patients with a TIA or infarct in the territory of the PCA with 16-multidetector-row CT angiography (CTA). Methods 82 patients (52 male; mean age = 64; range 19 to 90 years) with isolated homonymous hemianopia and/or a PCA infarct underwent CTA of the carotid artery and circle of Willis. Results A fetal origin of the PCA at the symptomatic side was present in 14 patients (17 %) and at the asymptomatic side in 18 patients (22%) (OR: 0.7; 95 % CI: 0.3 to 1.7). Severity of stenosis (NASCET criteria) of the ICA at the symptomatic side was &lt; 30%, 30-49% and &gt;= 50% in 72, 2 and 8 patients, respectively. Number and frequency of a fetal origin in these groups were 12 (17 %), 0 (0%) and 2 (25 %), respectively. There was no association between a severe carotid stenosis and a fetal origin of the PCA at the symptomatic side. Conclusions This study does not provide arguments for an increased risk of ischemic stroke in the territory of the PCA in patients with a fetal origin of the PCA. A few patients with a TIA or infarct in the territory of the PCA have a fetal origin of the PCA in combination with a high-grade stenosis of the ipsilateral ICA, but not more often than one would expect from chance. Nevertheless, these patients may benefit from carotid endarterectomy