Lena-Alexandra Beume

Massive exacerbation of multiple sclerosis after withdrawal and early restart of treatment with natalizumab

We present a 46-year-old woman with a relapse of multiple sclerosis (MS) that began 3 months after withdrawal from long-term treatment with natalizumab. Shortly after restart of a single dose of natalizumab she developed a fulminant MS rebound with stupor and tetraparesis. Cerebral MRI showed massive progression in the number of lesions and tumefactive lesions with ring gadolinium-enhancement. Stereotactic brain biopsy revealed acute demyelination and B-cell dominated inflammation. The patient improved during therapeutic plasma exchange. We speculate that early restart of natalizumab in the case of a relapse may worsen disease evolution possibly by modifying regulatory immune effector processes during an inflammatory rebound phase. A restart of natalizumab in MS patients suffering from a recent relapse or with signs of active inflammation should be considered with caution.

Processing of bilateral versus unilateral conditions: Evidence for the functional contribution of the ventral attention network

Processing of multiple or bilateral conditions presented simultaneously in both hemifields reflects the natural mode of perception in our multi-target environment, but is not yet completely understood. While region-of-interest based studies in healthy subjects reported single cortical areas as the right inferior parietal lobe (IPL) or temporoparietal junction (TPJ) to process bilateral conditions, studies in extinction patients with reduced ability in this regard suggested the right superior temporal cortex to hold a key role. The present fMRI study on healthy subjects aimed at resolving these discrepancies by contrasting bilateral versus unilateral visual conditions in a paradigm similar to the bed-side test for patients with visual extinction on a whole brain level. Additionally, reduced attentional capacity in spatial processing was investigated in normal aging. Processing of bilateral conditions compared to unilateral ones showed to require stronger activation of not one single cortical region but the entire right-lateralized ventral attention network, bilateral parietal and visual association areas. These results might suggest a conceptual difference between unilateral and bilateral spatial processing with the latter depending on additional anatomical and functional brain resources. Reduced attentional capacity in elderly subjects was associated with compensatory recruitment of contralateral functional homologues [left IPL, TPJ, frontal eye field (FEF)]. These data reveal the functional anatomy of our ability to visually process and respond to the entity of the environment and improve our understanding of neglect and extinction. Moreover, the data demonstrate that a restriction of the attentional capacity is based on processing limitations in the network of high-level cortical areas and not due to restriction in the primary sensory ones.

Olfactory hallucinations as primary symptom for ischemia in the right posterior insula.

A 55-year-old female presented with olfactory hallucinations of “burned hair” shortly before developing a sensorimotor hemiparesis of the left side and visuospatial neglect. On admission, her National Institutes of Health Stroke Scale score (NIHSS) was 11; her vital signs and the remainder of the physical exam were unremarkable. Cerebral MRI (1.5 Tesla, Siemens Avanto) showed an ischemic lesion with restricted diffusion involving about 20% of the right middle cerebral artery (MCA) territory. The infarcted area included the posterior insula and preand postcentral gyrus (Fig. 1A) and resulted from an occlusion of theM2 segment of the rightMCA. Intravenous thrombolysis (60 mg recombinant tissue plasminogen activator) was administered 90minutes

Activation of disease during therapy with alemtuzumab in 3 patients with multiple sclerosis

Objective To report 3 patients with multiple sclerosis showing severe activation of disease during immunotherapy with alemtuzumab. Methods Retrospective case series. Results Patient 1, a 21-year-old woman, developed severe cognitive impairment, sight deterioration, severe gait ataxia, urinary retention, and extensive progression of cerebral lesion load, including new lesions that exhibited gadolinium ring enhancement and dominance of CD19/20-positive B lymphocytes, 6 months after induction of alemtuzumab. Patient 2, a 28-year-old man, developed left-sided hemihypesthesia and ∼60 new cerebral and spinal lesions including lesions with gadolinium ring enhancement 6 months after induction of alemtuzumab. Patient 3, a 37-year-old woman, developed ataxia and numbness of the left thigh, 16 new gadolinium-positive supratentorial lesions, and partly ring-enhancing and dominance of CD19/20-positive B lymphocytes 6 months after induction of alemtuzumab. Conclusion This is a case series reporting severe activation of disease during immunotherapy with alemtuzumab. All patients showed onset of symptoms 6 months after induction of alemtuzumab, strikingly similar MRI lesion morphology, and unexpected high total B cell count, which may suggest a B-cell-mediated activation of disease. Whether this is due to different rates of B- and T cell repopulation has to be the subject of further research. Moreover, further effects on the interactions between the adaptive and innate immunity as well as between B and T cell lineages might explain the observed disease activation.