Cardiac sarcoidosis and neurosarcoidosis - multidisciplinary approach for diagnosis.

PURPOSE OF REVIEW: The current review aims to highlight the role of multidisciplinary approach in the diagnosis of patients with cardiac and neurosarcoidosis. Multidisciplinary approach integrates the available clinical information, imaging and histopathological results aiming to reach a definite or at least provisional diagnosis and allow appropriate management. Multidisciplinary approach is the reference standard for diagnosis of interstitial lung disease and should be strongly considered in complex clinical conditions such as cardiac sarcoidosis (CS) and neurosarcoidosis. RECENT FINDINGS: Histopathological confirmation of noncaseating granulomatous inflammation provides a definite diagnosis of sarcoidosis involving any organ. However, a provisional high confidence or even definite clinical diagnosis can be reached using multidisciplinary evaluation of all available evidence. The diagnosis of cardiac sarcoidosis and neurosarcoidosis requires the integration of different expertise based on the current diagnostic criteria sets. Identifying typical or at least compatible patterns on advanced imaging modalities (CMR and Fluro-Deoxy-Glucose Positron Emission Tomography (FDG-PET)) seems key for the diagnosis of CS, while a confident diagnosis of extra-cardiac disease supports an at least provisional diagnosis. Similarly, in neurosarcoidosis integrating compatible MRI appearances and cerebrospinal fluid results in patients with systemic sarcoidosis allows an at least provisional diagnosis. Exclusion of alternative differential diagnoses is crucial and requires high clinical suspicion, imaging review expertise and appropriate tests performance. SUMMARY: There have been considerable advances in the diagnostic approach of patients with cardiac and neurosarcoidosis. Multidisciplinary approach for both diagnosis and management is required to reach a confident clinical diagnosis and should be applied when possible.

Autologous Hematopoietic Stem Cell Transplantation in Active Multiple Sclerosis: A Real-world Case Series.

OBJECTIVE: To examine outcomes in people with multiple sclerosis (PwMS) treated with autologous hematopoietic stem cell transplantation (AHSCT) in a real-world setting. METHODS: This was a retrospective cohort study of PwMS treated with AHSCT at 2 centers in London, UK, consecutively between 2012 and 2019 who had ≥6 months of follow-up or died at any time. Primary outcomes were survival free of multiple sclerosis (MS) relapses, MRI new lesions, and worsening of Expanded Disability Status Scale (EDSS) score. Adverse events rates were also examined. RESULTS: The cohort includes 120 PwMS; 52% had progressive MS (primary or secondary) and 48% had relapsing-remitting MS. At baseline, the median EDSS score was 6.0; 90% of the evaluable cases showed MRI activity in the 12 months preceding AHSCT. Median follow-up after AHSCT was 21 months (range 6-85 months). MS relapse-free survival was 93% at 2 years and 87% at 4 years after AHSCT. No new MRI lesions were detected in 90% of participants at 2 years and in 85% at 4 years. EDSS score progression-free survival (PFS) was 75% at 2 years and 65% at 4 years. Epstein-Barr virus reactivation and monoclonal paraproteinemia were associated with worse PFS. There were 3 transplantation-related deaths within 100 days (2.5%), all after fluid overload and cardiac or respiratory failure. CONCLUSIONS: Efficacy outcomes of AHSCT in this real-world cohort are similar to those reported in more stringently selected clinical trial populations, although the risks may be higher. CLASSIFICATION OF EVIDENCE: This study is rated Class IV because of the uncontrolled, open-label design.

Development of Autoimmune Thyroid Disease in Multiple Sclerosis Patients Post-Alemtuzumab Improves Treatment Response.

CONTEXT: Alemtuzumab is an anti-CD52 monoclonal antibody used in the treatment of relapsing-remitting multiple sclerosis (MS). Between 20% and 40% of alemtuzumab-treated MS patients develop autoimmune thyroid disease (AITD) as a side effect. OBJECTIVE: The objective of this work is to determine whether MS disease progression following alemtuzumab treatment differs in patients who develop AITD compared to those who do not. DESIGN, SETTING, AND PATIENTS: A retrospective analysis of 126 patients with relapsing-remitting MS receiving alemtuzumab from 2012 to 2017 was conducted at a tertiary referral center. MAIN OUTCOME MEASURES: Thyroid status, new relapses, Expanded Disability Status Scale (EDSS) score change, and disability progression following alemtuzumab were evaluated. RESULTS: Twenty-six percent (33 out of 126, 25 female, 8 male) of alemtuzumab-treated patients developed AITD, 55% of which was Graves disease. EDSS score following alemtuzumab was reduced in patients who developed AITD compared to those who did not (median [interquartile range]; AITD: -0.25 [-1 to 0.5] vs non-AITD: 0 [1-0]. P = .007]. Multivariable regression analysis confirmed that the development of AITD was independently associated with EDSS score improvement (P = .011). Moreover, AITD patients had higher relapse-free survival following alemtuzumab (P = .023). There was no difference in the number of new focal T2 lesions and contrast-enhancing magnetic resonance imaging lesions developed following alemtuzumab between the 2 groups. CONCLUSION: Graves disease was the most common form of AITD developed by MS patients following alemtuzumab. This study suggests that MS patients who develop AITD may have an improved response to alemtuzumab, as measured by reduced disability and lower relapse rate.

A black mould death: A case of fatal cerebral phaeohyphomycosis caused by Cladophialophora bantiana.

Cladophialophora bantiana is a neurotropic mould and primary cause of cerebral phaeohyphomycoses, which presents with brain abscesses in both immunocompromised and immunocompetent individuals. It is associated with high mortality due to delay in diagnosis and absence of standardised therapy. We present a case of fatal cerebral phaeohyphomycosis in a 67-year-old Caucasian man. Diagnosis was achieved by histopathological examination of brain tissue followed by conventional culture and molecular identification. We highlight diagnostic and treatment challenges involved.

Anti-NMDAR encephalitis complicating pregnancy.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis was first reported in 2005 in four patients with ovarian teratomas; there have been many further cases reported since the antigen for the NMDAR antibody was confirmed in 2007. Patients characteristically have a well-defined set of features, characterised by psychiatric disturbance, seizures and cognitive disturbance, followed by movement disorders, disorders of consciousness and dysautonomia. To date, 14 cases of NMDAR encephalitis have been described in the context of pregnancy. We report a case of NMDAR encephalitis in a 34-year-old woman at 8 weeks' gestation. She had a turbulent clinical course and was initially admitted to a psychiatric unit. She was successfully treated with first-line immunomodulatory therapies and surgical resection of an ovarian teratoma. Following discharge she delivered a healthy baby and made a complete clinical recovery.

Motor phenotype and magnetic resonance measures of basal ganglia iron levels in Parkinson's disease.

BACKGROUND: In Parkinson's disease the degree of motor impairment can be classified with respect to tremor dominant and akinetic rigid features. While tremor dominance and akinetic rigidity might represent two ends of a continuum rather than discrete entities, it would be important to have non-invasive markers of any biological differences between them in vivo, to assess disease trajectories and response to treatment, as well as providing insights into the underlying mechanisms contributing to heterogeneity within the Parkinson's disease population. METHODS: Here, we used magnetic resonance imaging to examine whether Parkinson's disease patients exhibit structural changes within the basal ganglia that might relate to motor phenotype. Specifically, we examined volumes of basal ganglia regions, as well as transverse relaxation rate (a putative marker of iron load) and magnetization transfer saturation (considered to index structural integrity) within these regions in 40 individuals. RESULTS: We found decreased volume and reduced magnetization transfer within the substantia nigra in Parkinson's disease patients compared to healthy controls. Importantly, there was a positive correlation between tremulous motor phenotype and transverse relaxation rate (reflecting iron load) within the putamen, caudate and thalamus. CONCLUSIONS: Our findings suggest that akinetic rigid and tremor dominant symptoms of Parkinson's disease might be differentiated on the basis of the transverse relaxation rate within specific basal ganglia structures. Moreover, they suggest that iron load within the basal ganglia makes an important contribution to motor phenotype, a key prognostic indicator of disease progression in Parkinson's disease.

The effects of the dopamine agonist rotigotine on hemispatial neglect following stroke.

Hemispatial neglect following right-hemisphere stroke is a common and disabling disorder, for which there is currently no effective pharmacological treatment. Dopamine agonists have been shown to play a role in selective attention and working memory, two core cognitive components of neglect. Here, we investigated whether the dopamine agonist rotigotine would have a beneficial effect on hemispatial neglect in stroke patients. A double-blind, randomized, placebo-controlled ABA design was used, in which each patient was assessed for 20 testing sessions, in three phases: pretreatment (Phase A1), on transdermal rotigotine for 7-11 days (Phase B) and post-treatment (Phase A2), with the exact duration of each phase randomized within limits. Outcome measures included performance on cancellation (visual search), line bisection, visual working memory, selective attention and sustained attention tasks, as well as measures of motor control. Sixteen right-hemisphere stroke patients were recruited, all of whom completed the trial. Performance on the Mesulam shape cancellation task improved significantly while on rotigotine, with the number of targets found on the left side increasing by 12.8% (P = 0.012) on treatment and spatial bias reducing by 8.1% (P = 0.016). This improvement in visual search was associated with an enhancement in selective attention but not on our measures of working memory or sustained attention. The positive effect of rotigotine on visual search was not associated with the degree of preservation of prefrontal cortex and occurred even in patients with significant prefrontal involvement. Rotigotine was not associated with any significant improvement in motor performance. This proof-of-concept study suggests a beneficial role of dopaminergic modulation on visual search and selective attention in patients with hemispatial neglect following stroke.

Attention deficits following ADEM ameliorated by guanfacine.

The authors report here the case of a patient with severe deficits in arousal and sustained attention, associated with hemispatial neglect. These impairments were secondary to acute disseminated encephalomyelitis, with bilateral involvement of the medial nuclei and pulvinar of the thalamus. Treatment with the noradrenergic agonist guanfacine, previously used for attention deficits in attention deficit/hyperactivity disorder and stroke, was associated with a significant amelioration of both the spatial and sustained attention impairments in neglect. Guanfacine may prove to be a useful tool in the treatment of disorders of attention associated with neurological conditions.

Rehabilitation in practice: Hemispatial neglect: approaches to rehabilitation.

This series of articles for rehabilitation in practice aims to cover a knowledge element of the rehabilitation medicine curriculum. Nevertheless they are intended to be of interest to a multidisciplinary audience. The competency addressed in this article is 'The trainee consistently demonstrates a knowledge of the pathophysiology of various specific impairments including cognitive dysfunction including perception' and 'management approaches for specific impairments including cognitive dysfunction including perception'. The article focuses on hemispatial neglect as a common and difficult to manage problem in clinical practice.

Integration of goal- and stimulus-related visual signals revealed by damage to human parietal cortex.

Where we look is determined both by our current intentions and by the tendency of visually salient items to "catch our eye." After damage to parietal cortex, the normal process of directing attention is often profoundly impaired. Here, we tracked parietal patients' eye movements during visual search to separately map impairments in goal-directed orienting to targets versus stimulus-driven gaze shifts to salient but task-irrelevant probes. Deficits in these two distinct types of attentional selection are shown to be identical in both magnitude and spatial distribution, consistent with damage to a "priority map" that integrates goal- and stimulus-related signals to select visual targets. When goal-relevant and visually salient items compete for attention, the outcome depends on a biased competition in which the priority of contralesional targets is undervalued. On the basis of these findings, we further demonstrate that parietal patients' spatial bias (neglect) in goal-directed visual exploration can be corrected and even reversed by systematically manipulating the spatial distribution of stimulus salience in the visual array.

The functional role of the inferior parietal lobe in the dorsal and ventral stream dichotomy.

Current models of the visual pathways have difficulty incorporating the human inferior parietal lobe (IPL) into dorsal or ventral streams. Some recent proposals have attempted to integrate aspects of IPL function that were not hitherto dealt with well, such as differences between the left and right hemisphere and the role of the right IPL in responding to salient environmental events. However, we argue that these models also fail to capture adequately some important findings regarding the functions of the IPL. Here we critically appraise existing proposals regarding the functional architecture of the visual system, with special emphasis on the role of this region, particularly in the right hemisphere. We review evidence that shows the right IPL plays an important role in two different, but broadly complementary, aspects of attention: maintaining attentive control on current task goals as well as responding to salient new information or alerting stimuli in the environment. In our view, findings from functional imaging, electrophysiological and lesion studies are all consistent with the view that this region is part of a system that allows flexible reconfiguration of behaviour between these two alternative modes of operation. Damage to the right IPL leads to deficits in both maintaining attention and also responding to salient events, impairments that contribute to hemineglect, the classical syndrome that follows lesions of this region.

Treatment of attention deficits in neurological disorders.

PURPOSE OF REVIEW: Recent work has revealed the impact of deficits of attention on patients with neurological disorders. Here we discuss therapeutic interventions that have been used across a range of conditions, highlighting common themes both in the nature of the attention deficits and the strategies employed to treat them. RECENT FINDINGS: Cholinesterase inhibitors improve attention, as well as memory, in several conditions including cortical Lewy body disease, Parkinson's disease dementia, traumatic brain injury and Alzheimer's disease. Recent studies suggest that cholinergic stimulation may boost attention further if more specific nicotinic cholinergic agonists are used, or if cholinesterase inhibitors are combined with other agents. Monoaminergic drugs have been shown to improve attention in traumatic brain injury, attention-deficit hyperactivity disorder and hemispatial neglect following right-hemisphere stroke. New compounds targeting other neurotransmitter systems are currently being tested, while several types of behavioural intervention have shown promise, particularly in stroke patients. SUMMARY: Pharmacological and behavioural interventions can improve attention in neurological patients. In the future, optimum therapy may depend on careful delineation of the components of attention that are impaired as well as assessment of the potential for surviving brain regions to compensate for attention deficits.