Reversible cerebral vasoconstriction syndrome (RCVS) is a rare but increasingly recognized disorder with over 500 cases published in the literature. The condition is characterized by recurrent severe thunderclap headaches with or without other neurological symptoms and diffuse segmental narrowing of the cerebral arteries which is reversible within 3 months. RCVS may occur spontaneously but in over 50% of cases, it is associated with various other conditions, including vasoactive medications or illicit drugs and the post-partum state. One third to a half of cases develop hemorrhagic or ischemic brain lesions or a combination of both. Posterior reversible encephalopathy syndrome (PRES) often occurs in association with RCVS and the conditions are likely to share a common pathophysiology. The pathogenesis of RCVS remains uncertain but autonomic dysregulation, oxidative stress, and genetic predisposition are postulated. Significant differential diagnoses include subarachnoid hemorrhage (SAH) due to aneurysmal rupture, cervical artery dissection, and primary angiitis of the central nervous system (PACNS). Although there is no proven treatment, calcium channel antagonists including nimodipine and verapamil have been administered with reported reduction of headache intensity but without effect on the time course of cerebral vasoconstriction. Glucocorticoids have been reported as an independent predictor of worse outcome and should be avoided. The cornerstone of RCVS management remains largely supportive with bed rest and analgesics and removal of precipitating factors. Invasive neurointerventional techniques should be reserved for severe deteriorating cases. The condition is usually benign and self-limited and the majority of patients have a favorable outcome but around 5-10% are left with permanent neurological deficits and rare cases may die. This review details the importance of the early recognition of this increasingly described condition and current treatment recommendations.

BackgroundTrials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to determine if daily fluoxetine for 6 months after stroke improves functional outcome in Australasian and Vietnamese patients. MethodsAFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial conducted in 43 hospital stroke units in Australia (n=29), New Zealand (4), and Vietnam (10). Eligible patients were adults with a clinical diagnosis of stroke in the previous 2-15 days and a persisting neurological deficit. Patients were randomised via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20mg or matching placebo for 6 months. Patients, investigators and outcome assessors were masked to the treatment allocation. The primary outcome was functional outcome, measured by the modified Rankin scale (mRS), at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Analyses were according to the patient's treatment allocation. The trial is registered with the ACTRN registry, number 12611000774921. FindingsPowered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation 1280 patients were recruited in Australia (n=532), New Zealand (n=42) and Vietnam (n=706) between 11 January 2013 and 30 June 2019; 642 were allocated fluoxetine and 638 placebo. Adherence to trial medication (mean 167 [SD 48] days) was similar between groups. At 6 months, mRS data were available in 624 (97.2%) patients allocated fluoxetine and 632 (99.1%) placebo. The distribution of mRS categories at 6 months was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0.936, 95% CI 0.762-1.150; p=0.53), and consistent among all pre-defined subgroups. Compared to placebo, patients allocated fluoxetine had more falls (20 [3.12%] vs 7 [1.10%]; p=0.02), bone fractures (19 [2•96%] vs 6 [0.94%]; p=0.01) and epileptic seizures (10 [1.56%] vs 2 [0.31%]; p=0.04) at 6 months. InterpretationFluoxetine 20mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and seizures. These results do not support the use of fluoxetine to improve outcome after stroke.

Voluntary activity produces activity-dependent hyperpolarization of the active motor axons. The present study investigated whether this hyperpolarization produces conduction block in chronic inflammatory demyelinating polyneuropathy (CIDP). Studies were performed in 10 healthy control subjects, 7 patients with CIDP, and 3 patients with multifocal motor neuropathy. The compound muscle action potential (CMAP) of the abductor pollicis brevis was recorded in response to supramaximal stimuli to the median nerve at the wrist, alternating with measurements of axonal excitability. After a maximal voluntary contraction for 60 seconds, the amplitude of the maximal CMAP was significantly reduced in symptomatic CIDP patients by 40%, but there were only slight changes in the CMAPs of healthy controls, asymptomatic CIDP patients, and multifocal motor neuropathy patients. In symptomatic CIDP patients, the activity-dependent conduction block paralleled the activity-dependent hyperpolarization and was presumably precipitated by it. In these patients, the safety margin for impulse conduction was estimated to be about 12%. Activity-dependent conduction block may be clinically important in chronic demyelinating diseases and can be demonstrated electrophysiologically if testing occurs across pathological sites.

This study compared directly the post‐ischaemic behaviour of sensory and motor axons in the human median nerve, focusing on the excitability changes produced by ischaemia and its release and by continuous polarizing DC. The decrease in threshold during ischaemia for 13 min was greater, the post‐ischaemic increase in threshold was more rapid, and the return to the pre‐ischaemic excitability took longer in sensory axons. However, a transient depolarizing threshold shift developed in sensory axons a few minutes after release of ischaemia. This pattern could not be reproduced by polarizing currents designed to mimic the probable pump‐induced changes in membrane potential, even though the applied currents produced greater changes in threshold. Hyperpolarizing currents of equivalent intensity produced a greater increase in threshold for motor axons than sensory axons and, in studies of threshold electrotonus using graded hyperpolarizing DC, accommodation was greater in sensory than motor axons. The post‐ischaemic changes in threshold were not uniform for axons of different threshold, whether sensory or motor, the threshold increase was usually less prominent for low‐threshold axons. A transient post‐ischaemic depolarization could be produced in motor axons with ischaemia of 20 min duration. Greater ischaemic and post‐ischaemic changes in threshold for sensory axons could reflect greater dependence on the electrogenic Na+‐K+ pump to maintain resting membrane potential and/or greater extracellular K+ accumulation in ischaemic sensory axons. Inward K+ currents due to extracellular K+ accumulation would then be more likely to trigger a depolarizing shift in membrane potential, the degree of K+ accumulation and pump activity being dependent on the duration of ischaemia. In sensory axons the greater tendency to accommodate to hyperpolarizing stimuli presumably contributes to shaping their post‐ischaemic behaviour but is probably insufficient to explain why their behaviour differs from that of motor axons.

Threshold tracking was used to compare excitability properties (stimulus-response curves, strength-duration properties, recovery cycle and threshold electrotonus) of the median nerve in 11 patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and 25 healthy controls. Stimulus-response curves were significantly different: threshold was much higher, the slope of the curves reduced and the spread of the thresholds greater in the CIDP group. The strength-duration time constant (tau(SD)) was significantly shorter and the rheobase higher in the CIDP group. In the recovery cycle, the CIDP group had less refractoriness, supernormality and late subnormality than healthy controls, but the duration of the relatively refractory period was normal. These changes in tau(SD) and the recovery cycle were not those previously predicted. There were no consistent changes in threshold electrotonus, suggesting that, for the studied axons, there are no consistent changes in accommodation properties that depend on internodal conductances. It is difficult to explain these changes in excitability on the basis of a change in membrane potential, or solely as the result of demyelination, and it is possible that other morphological factors such as variable remyelination and inflammatory oedema affected axonal excitability in the patients.

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Voluntary activity produces activity‐dependent hyperpolarization of the active motor axons. The present study investigated whether this hyperpolarization produces conduction block in chronic inflammatory demyelinating polyneuropathy (CIDP). Studies were performed in 10 healthy control subjects, 7 patients with CIDP, and 3 patients with multifocal motor neuropathy. The compound muscle action potential (CMAP) of the abductor pollicis brevis was recorded in response to supramaximal stimuli to the median nerve at the wrist, alternating with measurements of axonal excitability. After a maximal voluntary contraction for 60 seconds, the amplitude of the maximal CMAP was significantly reduced in symptomatic CIDP patients by 40%, but there were only slight changes in the CMAPs of healthy controls, asymptomatic CIDP patients, and multifocal motor neuropathy patients. In symptomatic CIDP patients, the activity‐dependent conduction block paralleled the activity‐dependent hyperpolarization and was presumably precipitated by it. In these patients, the safety margin for impulse conduction was estimated to be about 12%. Activity‐dependent conduction block may be clinically important in chronic demyelinating diseases and can be demonstrated electrophysiologically if testing occurs across pathological sites. Ann Neurol 2000;48:826–832

Background: The ABCD