Martin Gizzi

Vestibular control of sympathetic activity. An otolith-sympathetic reflex in humans

It has been proposed that a vestibular reflex originating in the otolith organs and other body graviceptors modulates sympathetic activity during changes in posture with regard to gravity. To test this hypothesis, we selectively stimulated otolith and body graviceptors sinusoidally along different head axes in the coronal plane with off-vertical axis rotation (OVAR) and recorded sympathetic efferent activity in the peroneal nerve (muscle sympathetic nerve activity, MSNA), blood pressure, heart rate, and respiratory rate. All parameters were entrained during OVAR at the frequency of rotation, with MSNA increasing in nose-up positions during forward linear acceleration and decreasing when nose-down. MSNA was correlated closely with blood pressure when subjects were within ±90° of nose-down positions with a delay of 1.4 s, the normal latency of baroreflex-driven changes in MSNA. Thus, in the nose-down position, MSNA was probably driven by baroreflex afferents. In contrast, when subjects were within ±45° of the nose-up position, i.e., when positive linear acceleration was maximal along the naso-ocipital axis, MSNA was closely related to gravitational acceleration at a latency of 0.4 s. This delay is too short for MSNA changes to be mediated by the baroreflex, but it is compatible with the delay of a response originating in the vestibular system. We postulate that a vestibulosympathetic reflex, probably originating mainly in the otolith organs, contributes to blood pressure maintenance during forward linear acceleration. Because of its short latency, this reflex may be one of the earliest mechanisms to sustain blood pressure upon standing.

Orientation of human optokinetic nystagmus to gravity: a model-based approach

Optokinetic nystagmus (OKN) was induced by having subjects watch a moving display in a binocular, head-fixed apparatus. The display was composed of 3.3° stripes moving at 35°/s for 45 s. It subtended 88° horizontally by 72° vertically of the central visual field and could be oriented to rotate about axes that were upright or tilted 45° or 90°. The head was held upright or was tilted 45° left or right on the body during stimulation. Head-horizontal (yaw axis) and head-vertical (pitch axis) components of OKN were recorded with electro-oculography (EOG). Slow phase velocity vectors were determined and compared with the axis of stimulation and the spatial vertical (gravity axis). With the head upright, the axis of eye rotation during yaw axis OKN was coincident with the stimulus axis and the spatial vertical. With the head tilted, a significant vertical component of eye velocity appeared during yaw axis stimulation. As a result the axis of eye rotation shifted from the stimulus axis toward the spatial vertical. Vertical components developed within 1–2 s of stimulus onset and persisted until the end of stimulation. In the six subjects there was a mean shift of the axis of eye rotation during yaw axis stimulation of ≈ 18° with the head tilted 45° on the body. Oblique optokinetic stimulation with the head upright was associated with a mean shift of the axis of eye rotation toward the spatial vertical of 9.2°. When the head was tilted and the same oblique stimulation was given, the axis of eye rotation rotated to the other side of the spatial vertical by 5.4°. This counterrotation of the axis of eye rotation is similar to the “Müller (E) effect,” in which the perception of the upright is counterrotated to the opposite side of the spatial vertical when subjects are tilted in darkness. The data were simulated by a model of OKN with a “direct” and “indirect” pathway. It was assumed that the direct visual pathway is oriented in a body, not a spatial frame of reference. Despite the short optokinetic after-nystagmus time constants, strong horizontal to vertical cross-coupling could be produced if the horizontal and vertical time constants were in proper ratio and there were no suppression of nystagmus in directions orthogonal to the stimulus direction. The model demonstrates that the spatial orientation of OKN can be achieved by restructuring the system matrix of velocity storage. We conclude that an important function of velocity storage is to orient slow-phase velocity toward the spatial vertical during movement in a terrestrial environment.

Advances in thrombolytics for treatment of acute ischemic stroke

Over the past 50 years, thrombolytic agents have been devised with the aim of recanalizing occluded coronary vessels, and later on, applied in the setting of acute ischemic stroke. Pharmacologic agents have generally targeted the plasminogen–plasmin transformation, facilitating the natural process of fibrinolysis. Newer agents with varying degrees of fibrin selectivity and pharmacologic half-life have influenced both recanalization rates and hemorrhagic complications, inside and outside the CNS. Intra-arterial (IA) administration of fibrinolytic agents increases delivery of the drug to the thrombus at a higher concentration with smaller quantities and therefore lowers systemic exposure. Mechanical thrombus disruption or extraction allows for drug delivery to a greater surface area of the thrombus. Delays associated with IA therapy may worsen the risk/benefit ratio of thrombolysis; therefore, combinations of IA-IV treatments have been studied. To date, there are no direct comparative trials to show that endovascular administration is more efficacious or carries a lower risk of hemorrhagic complications than IV tissue plasminogen activator.

Neurosarcoidosis presenting as a tumour of the basal ganglia and brainstem: sequential MRI.

Neurosarcoidosis may spread from the basal leptomeninges via the Virchow-Robin spaces to form intraparenchymal masses. We present a case of sarcoidosis whose first presentation was that of secondary amenorrhoea without other neurological symptoms. Discovery of a mass invading the basal ganglia, hypothalamus, pituitary stalk and midbrain led to a search for systemic involvement. After the diagnosis was proven by mediastinal biopsy, steroids were used effectively to shrink the tumour. Sequential magnetic resonance imaging (MRI) studies demonstrate dramatic reduction in the mass over a six month period. A high index of suspicion for sarcoidosis in intracranial masses, particularly in young adults, is advocated.

Reversible cerebral vasoconstriction syndrome in a 35-year-old woman following hysterectomy and bilateral salpingo-oophorectomy

Introduction Reversible cerebral vasoconstriction syndromes (RCVS) have been documented to take place after an inciting event or illness. They present with headache, altered mental status and focal neurologic findings. The differential diagnosis includes primary angiitis of the central nervous system (PACNS) but one major clinical difference is that the symptoms of RCVS usually resolve within days or weeks whereas PACNS is often fatal. Females of childbearing age are most commonly affected with RCVS. Cases of reversible vasculopathy have also been reported in menopausal women. The hormonal and physiologic changes that take place during the postpartum period and menopause may not be very different from those that occur after a hysterectomy and oophorectomy. Methods A case is presented of a 35-year-old woman who underwent a hysterectomy with bilateral salpingo-oophorectomy and then began experiencing severe headaches, visual changes and hemi-sensory loss. Physical examination, imaging and laboratory findings were descriptive of RCVS, and the patients rapid recovery was consistent with the usual disease progression of a reversible vasculopathy. Conclusion A reversible cerebral vasoconstriction syndrome may occur in some circumstances after a hysterectomy with bilateral salpingo-oophorectomy. The mechanisms involved in the development of this condition are explained by current research concerning effects on the vasculature of sudden drops in estrogens and progesterones. More studies are required to further establish the pathophysiology, diagnosis and treatment of this condition.

The representation of the spatial vertical in human optokinetic nystagmus.

With our stimulus conditions we were unable to record more than 2-3 beats of OKAN; therefore direct comparison to the data recorded from monkeys is not possible. We did, however, see cross-coupling in OKN. In monkeys, cross-coupling predominates in OKAN, indicating that velocity storage underlies this phenomenon. We consistently saw the axis of response shift towards the spatial vertical. This implies that although OKAN was weak, velocity storage contributed a representation of the spatial vertical to OKN that is dependent on the axis of the head or body with respect to gravity.

Compliance with joint commission measures in state‐designated stroke centers

BACKGROUND Comparison of state-designated primary and comprehensive stroke centers (PSCs and CSCs) with regard to adherence to nationally accepted performance standards are scarce. The objective of this study was to examine if a significant association exists between level of designation and fulfillment of Joint Commission (JC) stroke core measures. METHODS A retrospective comparative data analysis of the New Jersey acute stroke registry for the calendar years 2010 and 2011 was performed. JC core measures were compared by hospital level (PSCs vs CSCs). Adjusted odds ratios (aOR) were estimated for association between hospital levels and fulfillment of JC core measures. Median door-to-thrombolytic time was also compared. RESULTS There were 36,892 acute stroke admissions. PSCs had 60% of the patients, whereas CSCs had 40%. Hemorrhagic stroke admissions were about 2 times more frequent at CSCs than PSCs (13.3% and 7.1%, respectively). CSCs adhered better to 6 of the 8 JC measures than PSCs. Of eligible patients, 19.5% received thrombolytic therapy at CSCs compared to 9.6% at PSCs, with a 44% difference in provision of thrombolytic therapy (aOR = 0.28, 95% confidence interval: 0.24-0.34). Median door-to-thrombolytic drug times was 65 minutes at CSCs compared to 74.0 minutes at PSCs (P < 0.0001). CONCLUSIONS New Jersey state-designated CSCs are better at adhering to the JC core stroke measures and have shorter door-to-thrombolytic drug times.