Ocular tremor in Parkinson’s disease: discussion, debate, and controversy

The identification of ocular tremor in a small cohort of patients with Parkinson’s disease (PD) had lay somewhat dormant until the recent report of a pervasive ocular tremor as a universal finding in a large PD cohort that was, however, generally absent from a cohort of age-matched healthy subjects. The reported tremor had frequency characteristics similar to those of PD limb tremor, but the amplitude and frequency of the tremor did not correlate with clinical tremor ratings. Much controversy ensued as to the origin of such a tremor, and specifically as to whether a pervasive ocular tremor was a fundamental feature of PD, or rather a compensatory eye oscillation secondary to a transmitted head tremor, and thus a measure of a normal vestibulo-ocular reflex. In this mini review, we summarize some of the evidence for and against the case for a pervasive ocular tremor in PD and suggest future experiments that may help resolve these conflicting opinions

The “broken escalator” phenomenon: Vestibular dizziness interferes with locomotor adaptation

BACKGROUND: Although vestibular lesions degrade postural control we do not know the relative contributions of the magnitude of the vestibular loss and subjective vestibular symptoms to locomotor adaptation. OBJECTIVE: To study how dizzy symptoms interfere with adaptive locomotor learning. METHODS: We examined patients with contrasting peripheral vestibular deficits, vestibular neuritis in the chronic stable phase (n = 20) and strongly symptomatic unilateral Meniere’s disease (n = 15), compared to age-matched healthy controls (n = 15). We measured locomotor adaptive learning using the “broken escalator” aftereffect, simulated on a motorised moving sled. RESULTS: Patients with Meniere’s disease had an enhanced “broken escalator” postural aftereffect. More generally, the size of the locomotor aftereffect was related to how symptomatic patients were across both groups. Contrastingly, the degree of peripheral vestibular loss was not correlated with symptom load or locomotor aftereffect size. During the MOVING trials, both patient groups had larger levels of instability (trunk sway) and reduced adaptation than normal controls. CONCLUSION: Dizziness symptoms influence locomotor adaptation and its subsequent expression through motor aftereffects. Given that the unsteadiness experienced during the “broken escalator” paradigm is internally driven, the enhanced aftereffect found represents a new type of self-generated postural challenge for vestibular/unsteady patients

Temporoparietal encoding of space and time during vestibular-guided orientation

When we walk in our environment, we readily determine our travelled distance and location using visual cues. In the dark, estimating travelled distance uses a combination of somatosensory and vestibular (i.e., inertial) cues. The observed inability of patients with complete peripheral vestibular failure to update their angular travelled distance during active or passive turns in the dark implies a privileged role for vestibular cues during human angular orientation. As vestibular signals only provide inertial cues of self-motion (e.g., velocity, °/s), the brain must convert motion information to distance information (a process called 'path integration') to maintain our spatial orientation during self-motion in the dark. It is unknown, however, what brain areas are involved in converting vestibular-motion signals to those that enable such vestibular-spatial orientation. Hence, using voxel-based lesion-symptom mapping techniques, we explored the effect of acute right hemisphere lesions in 18 patients on perceived angular position, velocity and motion duration during whole-body angular rotations in the dark. First, compared to healthy controls' spatial orientation performance, we found that of the 18 acute stroke patients tested, only the four patients with damage to the temporoparietal junction showed impaired spatial orientation performance for leftward (contralesional) compared to rightward (ipsilesional) rotations. Second, only patients with temporoparietal junction damage showed a congruent underestimation in both their travelled distance (perceived as shorter) and motion duration (perceived as briefer) for leftward compared to rightward rotations. All 18 lesion patients tested showed normal self-motion perception. These data suggest that the cerebral cortical regions mediating vestibular-motion ('am I moving?') and vestibular-spatial perception ('where am I?') are distinct. Furthermore, the congruent contralesional deficit in time (motion duration) and position perception, seen only in temporoparietal junction patients, may reflect a common neural substrate in the temporoparietal junction that mediates the encoding of motion duration and travelled distance during vestibular-guided navigation. Alternatively, the deficits in timing and spatial orientation with temporoparietal junction lesions could be functionally linked, implying that the temporoparietal junction may act as a cortical temporal integrator, combining estimates of self-motion velocity over time to derive an estimate of travelled distance. This intriguing possibility predicts that timing abnormalities could lead to spatial disorientation

Progression of endothelial dysfunction, atherosclerosis, and arterial stiffness in stable kidney transplant patients: a pilot study.

BACKGROUND: Kidney transplant patients suffer from vascular abnormalities and high cardiovascular event rates, despite initial improvements post-transplantation. The nature of the progression of vascular abnormalities in the longer term is unknown. This pilot study investigated changes in vascular abnormalities over time in stable kidney transplant patients long after transplantation. METHODS: Brachial artery flow-mediated dilation (FMD), nitroglycerin-mediated dilation, carotid-femoral pulse wave velocity (cf-PWV), ankle-brachial pressure index, and common carotid artery intima-media thickness (CCA-IMT) were assessed in 18 kidney transplant patients and 17 controls at baseline and 3-6 months after. RESULTS: There was no difference in age (51 ± 13 vs. 46 ± 11; P = 0.19), body mass index (26 ± 5 vs. 25 ± 3; P = 0.49), serum cholesterol (4.54 ± 0.96 vs. 5.14 ± 1.13; P = 0.10), systolic blood pressure (BP) (132 ± 12 vs. 126 ± 12; P = 0.13), diastolic BP (82 ± 9 vs. 77 ± 8; P = 0.10), or diabetes status (3 vs. 0; P = 0.08) between transplant patients and controls. No difference existed in vascular markers between patients and controls at baseline. In transplant patients, FMD decreased (- 1.52 ± 2.74; P = 0.03), cf-PWV increased (0.62 ± 1.06; P = 0.03), and CCA-IMT increased (0.35 ± 0.53; P = 0.02). No changes were observed in controls. CONCLUSION: Markers of vascular structure and function worsen in the post-transplant period on long-term follow-up, which may explain the continued high cardiovascular event rates in this population

Acute positional vertigo in the emergency department—peripheral vs. central positional nystagmus

INTRODUCTION: Benign paroxysmal positional vertigo (BPPV) is the most common cause of positional vertigo. However, positional vertigo can also be due to diseases affecting the central vestibular pathways, such as vestibular migraine. Accurate and timely diagnosis enables effective triage and management. OBJECTIVES: o evaluate diagnoses made by emergency clinicians compared to acute vertigo specialists, in patients presenting to an emergency department (ED) with positional vertigo. METHODS: Following routine ED care, patients with a primary complaint of dizziness, vertigo, light-headedness or unsteadiness, underwent detailed neuro-otological assessment by acute vertigo specialists. Demographics and final diagnoses were recorded and analyzed. RESULTS: Of 71 consented patients (21−91 years; mean 56 years, ±16.7 years, 40 females), ED identified 13 with a peripheral cause of positional vertigo (mean 48.85 years, ±16.19, 8 females). Central positional nystagmus was not noted in any of the patients with positional vertigo seen by the ED clinicians. Acute vertigo specialists diagnosed nine patients with BPPV (age range 50-88 years, mean 66 years, ±12.22, 5 females), and six with central positional nystagmus (age range 23−59 years, mean 41.67 years, ±15.78, 6 females). CONCLUSION: Positional vertigo should be assessed with positional maneuvers such as Dix-Hallpike and Roll tests in the ED to identify peripheral and central nystagmus features. Central causes are more common in younger females, with the presence of vomiting, and/or a background of motion sensitivity

Neurological update: dizziness

The diagnosis and management of vertigo remains a challenge for clinicians, including general neurology. In recent years there have been advances in the understanding of established vestibular syndromes, and the development of treatments for existing vestibular diagnoses. In this ‘update’ I will review how our understanding of previously “unexplained” dizziness in the elderly is changing, explore novel insights into the pathophysiology of vestibular migraine, and its relationship to the newly coined term ‘persistent postural perceptual dizziness’, and finally discuss how a simple bedside oculomotor assessment may help identify vestibular presentations of stroke

Why do patients with Parkinson's disease fall? A cross-sectional analysis of possible causes of falls.

Background: Falls in Parkinson’s disease (PD) are associated with significant injury, disability, hospitalization, and reduced quality of life. Aims: To identify modifiable medical causes of falls in a cohort of PD patients. Methods: Eighty seven PD patients were interviewed and examined using validated scales assessing motor and nonmotor aspects of PD, comorbidities and medication use. The frequency of falls in the last month was the primary outcome measure. Falls were hypothesized to be associated with increasing age, advanced motor severity, particularly axial features (e.g., freezing and postural instability), and dyskinesia. Nonmotor features hypothesized to be associated with falls included; cognitive impairment, psychosis, sleep disorders, cardiovascular dysfunction, and ophthalmological and medical comorbidities. Results: Fallers had longer disease duration, higher Levodopa-equivalent doses, greater ‘On’ time with dyskinesia (all P<0.005), and higher scores on some Movement Disorder Society-Unified Parkinson’s Disease Rating Scale items, particularly axial scores. However, patients with falls did not differ from non-fallers in age or overall motor UPDRS scores. Severity of psychosis, executive cognitive impairment, autonomic (particularly cardiovascular) dysfunction and sleep disturbances (particularly REM sleep behavioral disorder) were significantly associated with falls (all P<0.005). Fallers more frequently reported use of antidepressants (both tricyclics and SSRIs) and neuroleptics (P<0.001), but not hypnotics. There was no difference in medical comorbidities, ophthalmological assessments, fatigue, and apathy scores between the groups. In logistic regression analysis, cardiovascular dysfunction, antidepressant use, and REM sleep behavioral disorder were significantly associated with falls. Conclusions: The causes of falls in PD are multifactorial and extend beyond motor impairment and dyskinesia; addressing these in patients already treated with dopaminergic medications has the potential to improve this important complication of PD

Cranial functional (psychogenic) movement disorders

Functional (psychogenic) neurological symptoms are frequently encountered in neurological practice. Cranial movement disorders—affecting the eyes, face, jaw, tongue, or palate—are an under-recognised feature of patients with functional symptoms. They can present in isolation or in the context of other functional symptoms; in particular, for functional eye movements, positive clinical signs such as convergence spasms can be triggered by the clinical examination. Although the specialty of functional neurological disorders has expanded, appreciation of cranial functional movement disorders is still insufficient. Identification of the positive features of cranial functional movement disorders such as convergence and unilateral platysmal spasm might lend diagnostic weight to a suspected functional neurological disorder. Understanding of the differential diagnosis, which is broad and includes many organic causes (eg, stroke), is essential to make an early and accurate diagnosis to prevent complications and initiate appropriate management. Increased understanding of these disorders is also crucial to drive clinical trials and studies of individually tailored therapies

Video head impulse testing: Pitfalls in neurological patients

The video head impulse test (vHIT) assesses the vestibulo-ocular reflex (VOR) during a rapid high-velocity low amplitude (10°–20°) head rotation. Patients with peripheral vestibulopathy have a reduced VOR gain with corrective catch-up saccades during the head turn. There are several pitfalls, mainly technical, which may interfere with interpretation of vHIT data. In addition, intrusive eye movement disorders such as spontaneous nystagmus that affect normal eye position and tracking can affect the vHIT results. To date there has been little study of neurological saccadic eye movements that may interfere with the interpretation of vHIT data. Here, in ten patients with a range of central neurological disorders, we describe oculomotor abnormalities on vHIT in the presence of normal range VOR gain values, recorded at a tertiary vestibular neurology service