Eye movements serve vision in orienting gaze toward an object of interest in order to place its image simultaneously on both foveas and in stabilizing gaze relative to the environment in order to ...maintain fixation on the object of interest, even in the case of body displacement. Disorders of eye movements can interfere with ocular alignment and/or monocular motility, and result in diplopia, which is the most common symptom. Eye movement disorders can also interfere with binocular motility without ocular misalignment and result in gaze palsy. Finally, disorders of eye movement can interfere with ocular stability during fixation or body displacement and result in oscillopsia, which is an illusion of an unstable visual world. A systematic examination of eye movements should be part of the neurological exam in order to detect asymptomatic manifestations that can help for the diagnosis of multiple neurological pathologies. In the case of eye movement disorders, the goals of the examination are to precisely characterize the disorder of motility, alignment, or stability, in order to finally localize anatomically the lesion among the peripheral ocular motor system or the more complex central eye movement neural network and suggest mechanisms and etiologies. In this review, we are describing the standard methods of ocular motor examination, including a “general” approach to any ocular motor assessment, and also the specific approaches to evaluating ocular misalignment, difficulty moving both eyes, and finally unstable gaze. This article will include practical tips on how to perform the tests most effectively or how to interpret the clinical signs elicited.
Hypertrophic degeneration of the inferior olive is mainly observed in patients developing palatal tremor (PT) or oculopalatal tremor (OPT). This syndrome manifests as a synchronous tremor of the ...palate (PT) and/or eyes (OPT) that may also involve other muscles from the branchial arches. It is associated with hypertrophic inferior olivary degeneration that is characterized by enlarged and vacuolated neurons, increased number and size of astrocytes, severe fibrillary gliosis, and demyelination. It appears on MRI as an increased T2/FLAIR signal intensity and enlargement of the inferior olive. There are two main conditions in which hypertrophic degeneration of the inferior olive occurs. The most frequent, studied, and reported condition is the development of PT/OPT and hypertrophic degeneration of the inferior olive in the weeks or months following a structural brainstem or cerebellar lesion. This "symptomatic" condition requires a destructive lesion in the Guillain-Mollaret pathway, which spans from the contralateral dentate nucleus
the brachium conjunctivum and the ipsilateral central tegmental tract innervating the inferior olive. The most frequent etiologies of destructive lesion are stroke (hemorrhagic more often than ischemic), brain trauma, brainstem tumors, and surgical or gamma knife treatment of brainstem cavernoma. The most accepted explanation for this symptomatic PT/OPT is that denervated olivary neurons released from inhibitory inputs enlarge and develop sustained synchronized oscillations. The cerebellum then modulates/accentuates this signal resulting in abnormal motor output in the branchial arches. In a second condition, PT/OPT and progressive cerebellar ataxia occurs in patients without structural brainstem or cerebellar lesion, other than cerebellar atrophy. This syndrome of progressive ataxia and palatal tremor may be sporadic or familial. In the familial form, where hypertrophic degeneration of the inferior olive may not occur (or not reported), the main reported etiologies are Alexander disease, polymerase gamma mutation, and spinocerebellar ataxia type 20. Whether or not these are associated with specific degeneration of the dentato-olivary pathway remain to be determined. The most symptomatic consequence of OPT is eye oscillations. Therapeutic trials suggest gabapentin or memantine as valuable drugs to treat eye oscillations in OPT.
The syndrome of cerebellar ataxia with neuropathy and bilateral vestibular areflexia (CANVAS) has emerged progressively during the last 30 years. It was first outlined by the ...neurootology/neurophysiology community in the vestibular areflexic patients, through the description of patients slowly developing late-onset cerebellar ataxia and bilateral vestibulopathy. The characteristic deficit of visuo-vestibulo-ocular reflex (VVOR) due to the impaired slow stabilizing eye movements was put forward and a specific disease subtending this syndrome was suggested. The association to a peripheral sensory axonal neuropathy was described later on, with neuropathological studies demonstrating that both sensory neuropathy and vestibular areflexia were diffuse ganglionopathy. Clinical and electrophysiological criteria of CANVAS were then proposed in 2016. Besides the classical triad, frequent chronic cough, signs of dysautonomia and neurogenic pains were frequently observed. From the beginning of published cohorts, sporadic as well as familial cases were reported, the last suggestive of an autosomal recessive mode of transmission. The genetic disorder was discovered in 2019, under the form of abnormal biallelic expansion in the replication factor C subunit 1 (RFC1) in a population of late-onset ataxia. This pathological expansion was found in 100% of the familial form and 92% of sporadic ones when the triad was complete. But using the genetic criteria, the phenotype of CANVAS seems to expand, for exemple including patients with isolated neuronopathy. We propose here to review the clinical, electrophysiological, anatomical, genetic aspect of CANVAS in light of the recent discovery of the genetic aetiology, and discuss differential diagnosis, neuropathology and physiopathology.
Objective
To compare CSF biomarkers’ levels in patients suffering from anti-Leucine-rich Glioma-Inactivated 1 (LGI1) encephalitis to neurodegenerative Alzheimer’s disease (AD), Creutzfeldt–Jakob’s ...disease (CJD) and primary psychiatric (PSY) disorders.
Methods
Patients with LGI1 encephalitis were retrospectively selected from the French Reference Centre database between 2010 and 2019 and enrolled if CSF was available for biomarkers analysis including total tau (T-tau), phosphorylated tau (P-tau), amyloid-beta Aβ1-42, and neurofilaments light chains (Nf L). Samples sent for biomarker determination as part of routine practice, and formally diagnosed as AD, CJD, and PSY, were used as comparators.
Results
Twenty-four patients with LGI1 encephalitis were compared to 39 AD, 20 CJD and 20 PSY. No significant difference was observed in T-tau, P-tau, and Aβ1-42 levels between LGI1 encephalitis and PSY patients. T-Tau and P-Tau levels were significantly lower in LGI1 encephalitis (231 and 43 ng/L) than in AD (621 and 90 ng/L,
p
< 0.001) and CJD patients (4327 and 55 ng/L,
p
< 0.001 and
p
< 0.01). Nf L concentrations of LGI1 encephalitis (2039 ng/L) were similar to AD (2,765 ng/L) and significantly higher compared to PSY (1223 ng/L,
p
< 0.005), but significantly lower than those of CJD (13,457 ng/L,
p
< 0.001). Higher levels of Nf L were observed in LGI1 encephalitis presenting with epilepsy (3855 ng/L) compared to LGI1 without epilepsy (1490 ng/L,
p
= 0.02). No correlation between CSF biomarkers’ levels and clinical outcome could be drawn.
Conclusion
LGI encephalitis patients showed higher Nf L levels than PSY, comparable to AD, and even higher when presenting epilepsy suggesting axonal or synaptic damage linked to epileptic seizures.
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system leading to disability, especially in young patients. Acute or chronic lesions of MS within the brainstem and the ...cerebellum frequently result in ocular motor disorders.
This review encompasses the spectrum of ocular motor disorders in patients with MS emphasizing prevalence, examination findings, diagnostic features, functional consequences, classification of MS course, and management of these disturbances of ocular motility.
Ocular motor manifestations of MS can occur acutely in relapse or chronically, the latter as a consequence of previous relapses or as a chronic course of the disease. The most frequent and specific acute ocular motor manifestation is uni- or bilateral internuclear ophthalmoplegia (INO). The most frequent chronic manifestations include INO and cerebellar ocular motor disorders such as gaze-evoked nystagmus, saccadic hypermetria, and lack of vestibulo-ocular reflex inhibition. The most disabling syndrome is pendular nystagmus.
The high prevalence of ocular motor manifestations emphasizes the importance of neuro-ophthalmological examination among patients with MS. Because chronic manifestations may cause minimal or no symptoms, a systematic investigation of the most common manifestations should be performed in daily practice. Appropriate treatment may improve visual outcome in some of these ocular motor disorders.
The vestibular system has widespread connections in the central nervous system. Several activation loci following vestibular stimulations have been notably reported in deep, limbic areas that are ...otherwise difficult to reach and modulate in healthy subjects. Following preliminary evidence, suggesting that such stimulations might affect mood and affective processing, we wondered whether the vestibular system is also involved in motivation. Evolutionary accounts suggest that visuo-vestibular mismatches might have a role in preventing the search for and exploitation of goods that previously resulted in aversive reactions, as they would be a fine warning signal which follows the contact with or ingestion of noxious neurotoxins. The first question was thus whether vestibular stimulation alters sensitivity to reward. Secondly, we sought to assess whether attention is allocated in space differently when cued by highly motivational stimuli, and if this interplay is further modulated by the vestibular system. In order to evaluate both motivational and attentional assets, we administered a Posner-like cueing task to 30 healthy subjects concurrently receiving sham or galvanic vestibular stimulation (GVS; Left-Anodal and Right-Anodal configurations). The participants had to discriminate targets appearing in either exogenously cued or uncued locations (50% validity); cues predicted the amount of points (0, 2, or 10) and thus money that they could earn for a correct response. The results highlight a robust inhibition of return (IOR) (faster responses for invalidly-cued targets) which was not modulated by different levels of reward or GVS. Across all stimulation sessions, rewards exerted a powerful beneficial effect over performance: reaction times were faster when rewards were at stake. However, this effect was largest in sham, but greatly reduced in GVS conditions, most notably with the Right-Anodal configuration. This is the first evidence for a decreased sensitivity to rewards causally induced by a perturbation of the vestibular system. While future studies will shed light on its neural underpinnings and clinical implications, here we argue that GVS could be a safe and promising way to enrich our understanding of reward processes and eventually tackle the management of patients with aberrant sensitivity to rewards.
Considerable progress has been made in developing models of cerebellar function in sensorimotor control, as well as in identifying key problems that are the focus of current investigation. In this ...consensus paper, we discuss the literature on the role of the cerebellar circuitry in motor control, bringing together a range of different viewpoints. The following topics are covered: oculomotor control, classical conditioning (evidence in animals and in humans), cerebellar control of motor speech, control of grip forces, control of voluntary limb movements, timing, sensorimotor synchronization, control of corticomotor excitability, control of movement-related sensory data acquisition, cerebro-cerebellar interaction in visuokinesthetic perception of hand movement, functional neuroimaging studies, and magnetoencephalographic mapping of cortico-cerebellar dynamics. While the field has yet to reach a consensus on the precise role played by the cerebellum in movement control, the literature has witnessed the emergence of broad proposals that address cerebellar function at multiple levels of analysis. This paper highlights the diversity of current opinion, providing a framework for debate and discussion on the role of this quintessential vertebrate structure.
Purpose
The management of pituitary apoplexy, a rare emergency neuroendocrine condition, is controversial. The aim of the present study is to compare the outcomes of patients with pituitary apoplexy ...managed either by a conservative or surgical approach.
Methods
A retrospective cohort study including patients diagnosed between 2007 and 2018 in a tertiary French university hospital. Pituitary Apoplexy Score (PAS) was retrospectively applied in the perspective of therapeutic decision support.
Results
Forty-six patients were treated for pituitary apoplexy either with conservative management (
n
= 27) or surgery (
n
= 19). At initial evaluation, visual field defects (VFD) and visual acuity impairment were more frequent in patients from the surgery group. At 1 year there were no statistical differences in the rates of complete/near-complete resolution of VFD (100 vs. 91.7%), visual acuity impairment (100 vs. 87.5%), and cranial nerve palsies (83.3 vs. 100%), between conservative and surgical treatment groups. There were more endocrine deficits at 1 year in the surgical group (
p
= 0.029). PAS (
n
= 41) was 3.4 on average in the early surgery group and 1.3 in the conservative treatment/delayed surgery group. Among patients with a score < 4, 31.3% were operated at first line and did not present better outcomes than patients managed conservatively. In all, 88.9% of patients with a score ≥ 4 underwent surgery.
Conclusions
PAS may be a reliable parameter for defining therapeutic strategy. Patients with non-severe and nonprogressive neuro-ophthalmological deficits can be managed conservatively without negative impact on outcomes, thus surgery should be reserved only for those patients with a PAS ≥ 4.
To identify initial features associated with significant recovery in patients with Graves’ disease dysthyroid optic neuropathy (DON) treated according to EUGOGO guidelines by intravenous ...glucocorticoids (ivGC) and decompression surgery in first and second-line, respectively.
Consecutive patients referred to our expert multidisciplinary consultation over a 6-year period underwent systematic exploration: endocrine assessment, ophthalmic examination and radiological exploration. Visual recovery, based on best-corrected visual acuity (BCVA) and visual field (VF), were evaluated at baseline, 1week and 6months. Baseline parameters were then tested for prognostic value on univariate and multivariate analyses.
Thirty-eight patients (69 eyes) with DON were included. Significant recovery at 6months was found in 48/69 eyes (70%), partial recovery in 18/69 (26%), and no recovery in 3/69 (4%). Fifty-one eyes (28 patients) required surgical decompression after ivGC. These patients showed more severe presentation at diagnosis, had received significantly less GC for Graves’ orbitopathy before onset of DON, and showed greater fat prolapse on CT scans compared to non-operated patients. On multivariate analysis, male gender (P=0.001), cumulative GC dose>1g before DON diagnosis (P=0.048) and initial BCVA≤0.3 (P=0.004) were significantly associated with better outcomes, whereas Clinical Activity Score>5 (P=0.013) was associated with a poorer outcome.
This study confirms a generally favorable 6-month recovery rate in DON treated according to EUGOGO guidelines and provides new information on baseline predictors of poor evolution. These results may help the respective indications for medical and surgical treatment to be more effectively combined in the future.
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