Osteoporosis and fracture risk: a practical guide for neurologists.

Many people with neurological disorders are at high risk of osteoporosis and fragility fractures. Such fractures are a leading cause of disability and premature mortality. There are various underlying mechanisms, including reduced bone mineral density from biomechanical factors (eg, reduced muscle strength), inflammation and/or medications such as glucocorticoids, together with an increased risk of falls.

Insights from DCE-MRI: blood-brain barrier permeability in the context of MS relapses and methylprednisolone treatment.

Background: Detecting multiple sclerosis (MS) relapses remains challenging due to symptom variability and confounding factors, such as flare-ups and infections. Methylprednisolone (MP) is used for severe relapses, decreasing the number of contrast-enhancing lesions on MRI. The influx constant (K) derived from dynamic contrast-enhanced MRI (DCE-MRI), a marker of blood-brain barrier (BBB) permeability, has shown promise as a predictor of disease activity in relapsing-remitting MS (RRMS).

Measurement variability of blood-brain barrier permeability using dynamic contrast-enhanced magnetic resonance imaging.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is used to quantify the blood-brain barrier (BBB) permeability-surface area product. Serial measurements can indicate changes in BBB health, of interest to the study of normal physiology, neurological disease, and the effect of therapeutics. We performed a scan-rescan study to inform both sample size calculation for future studies and an appropriate reference change value for patient care.

Erythrocyte deformability correlates with systemic inflammation.

Recent evidence suggests that systemic conditions, particularly those associated with inflammation, can affect erythrocyte deformability in the absence of haematological conditions. In this exploratory study, we investigated the relationship between systemic inflammatory status and erythrocyte deformability (using osmotic gradient ektacytometry) in a heterogenous study population consisting of individuals with no medical concerns, chronic conditions, and acute illness, providing a wide range of systemic inflammation severity. 22 participants were included in a prospective observational study.

Mild Systemic Inflammation Increases Erythrocyte Fragility.

There is growing evidence that inflammation impairs erythrocyte structure and function. We assessed the impact of mild systemic inflammation on erythrocyte fragility in three different settings. In order to investigate causation, erythrocyte osmotic fragility was measured in mice challenged with a live attenuated bacterial strain to induce low-grade systemic inflammation; a significant increase in erythrocyte osmotic fragility was observed.

Systemic inflammation associates with and precedes cord atrophy in progressive multiple sclerosis.

In preclinical models of multiple sclerosis, systemic inflammation has an impact on the compartmentalized inflammatory process within the central nervous system and results in axonal loss. It remains to be shown whether this is the case in humans, specifically whether systemic inflammation contributes to spinal cord or brain atrophy in multiple sclerosis. Hence, an observational longitudinal study was conducted to delineate the relationship between systemic inflammation and atrophy using magnetic resonance imaging: the SIMS (Systemic Inflammation in Multiple Sclerosis) study.

Systemic infection drives urgent care needs and outcome in adults with long-term neurological conditions.

It is estimated that 1 in 6 people are living with a long-term neurological condition (LTNC). Although it is likely that systemic infections are a common trigger for urgent tertiary care needs in LTNCs, there is a lack of data. Yet this is important since systemic infections are a modifiable risk factor, and hence the motivation for a formal evaluation.

Blood-brain barrier permeability changes in the first year after alemtuzumab treatment predict 2-year outcomes in relapsing-remitting multiple sclerosis.

Background: In relapsing-remitting multiple sclerosis (RRMS), early disease control reduces the risk of permanent disability. The blood-brain barrier (BBB) is compromised in MS, and its permeability is a potential biomarker.

Objective: To investigate BBB permeability measured by MRI as a marker of alemtuzumab efficacy.

Gadolinium enhancement of cranial nerves: Implications for interstitial fluid drainage from brainstem into cranial nerves in humans.

Drainage of interstitial fluid and solutes from the brainstem has not been well studied. To map one drainage pathway in the human brainstem, we took advantage of the focal blood-brain barrier disruption occurring in a multiple sclerosis brainstem lesion, coupled with intravenous injection of gadolinium, which simulates an intraparenchymal injection of gadolinium tracer within the restricted confines of this small brain region. Using high-resolution MRI, we show how it is possible for interstitial fluid to drain into the adjacent trigeminal and oculomotor nerves, in keeping with a pathway of communication between the extracellular spaces of the brainstem and cranial nerve parenchyma.

COVID-19 Encephalitis with SARS-CoV-2 Detected in Cerebrospinal Fluid Presenting as a Stroke Mimic.

We report the case of a 35-year-old male with COVID-19 encephalitis presenting as a stroke mimic with sudden-onset expressive and receptive dysphasia, mild confusion and right arm incoordination. The patient received thrombolysis for a suspected ischaemic stroke, but later became febrile and SARS-CoV-2 was detected in cerebrospinal fluid. Electroencephalography demonstrated excess in slow waves, but neuroimaging was reported as normal.

Physical activity monitoring to assess disability progression in multiple sclerosis.

Background: Clinical outcome measurement in multiple sclerosis (MS) usually requires a physical visit. Remote activity monitoring (RAM) using wearable technology provides a rational alternative, especially desirable when distance is involved or in a pandemic setting.

Objective: To validate RAM in progressive MS using (1) traditional psychometric methods (2) brain atrophy.

High-Throughput Urinary Neopterin-to-Creatinine Ratio Monitoring of Systemic Inflammation.

Background: Systemic inflammation is a marker of ill health and has prognostic implications in multiple health settings. Urinary neopterin is an excellent candidate as a nonspecific marker of systemic inflammation. Expression as urinary neopterin-to-creatinine ratio (UNCR) normalizes for urinary hydration status.

Blood-brain barrier permeability measured using dynamic contrast-enhanced magnetic resonance imaging: a validation study.

Key Points: The blood-brain barrier (BBB) is an important and dynamic structure which contributes to homeostasis in the central nervous system. BBB permeability changes occur in health and disease but measurement of BBB permeability in humans is not straightforward. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can be used to model the movement of gadolinium contrast into the brain, expressed as the influx constant K .

Permeability of the blood-brain barrier predicts no evidence of disease activity at 2 years after natalizumab or fingolimod treatment in relapsing-remitting multiple sclerosis.

Objective: To investigate whether blood-brain barrier (BBB) permeability, as measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), can provide early detection of suboptimal treatment response in relapsing-remitting multiple sclerosis (RRMS).

Methods: Thirty-five RRMS patients starting on fingolimod or natalizumab, drugs with a common effect of decreasing lymphocyte influx into the central nervous system, were scanned with DCE-MRI at 3T prior to treatment and at 3 and 6 months posttreatment. We calculated the influx constant K , a measure of BBB permeability, using the Patlak model.

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We describe corticosteroid-responsive focal granulomatous encephalitis as a manifestation of herpes simplex virus (HSV) type 1 disease in the brain: something easily missed and easily treated. Two adult cases presented with cognitive symptoms progressing over weeks, despite aciclovir treatment. Brain imaging showed temporal lobe abnormalities, with gadolinium enhancement but no abnormal diffusion restriction.

The blood-brain barrier in systemic inflammation.

The blood-brain barrier (BBB) plays a key role in maintaining the specialized microenvironment of the central nervous system (CNS), and enabling communication with the systemic compartment. BBB changes occur in several CNS pathologies. Here, we review disruptive and non-disruptive BBB changes in systemic infections and other forms of systemic inflammation, and how these changes may affect CNS function in health and disease.

Differential diagnosis of finger drop.

Finger drop is a useful clinical sign which is easy to elicit. This article presents a logical approach for assessing patients with finger drop and outlines the important causes, and how to differentiate them. Patients with finger drop may present either to orthopedic surgeons or to neurologists, and both specialists should be aware of important diagnoses in their complementary fields.

Pendular nystagmus associated with venlafaxine overdose: a forme fruste of the serotonin syndrome?

We describe a case of pendular nystagmus as a previously unreported side effect of venlafaxine, and speculate to its importance in the recognition of the serotonin syndrome. In particular, we discuss the importance of identifying incomplete forms of the syndrome, such as those presenting with predominantly ocular manifestations, as is in our case.