Saccadic Intrusions Research Articles

Oculomotor and Vestibular Deficits in Friedreich Ataxia - Systematic Review and Meta-Analysis of Quantitative Measurements.

Disease-specific oculomotor assessments play a crucial role in the early diagnosis of hereditary cerebellar ataxias. Whereas several studies have reported on quantitative oculomotor and vestibular measurements in Friedreich's Ataxia (FRDA), the value of specific oculomotor paradigms remains unclear. We aimed to address this knowledge gap through a systematic literature review and providing disease-specific recommendations for a tailored set of eye-movement recordings in FRDA. MEDLINE and Embase were searched for studies reporting on quantitative oculomotor and/or vestibular measurements in FRDA-patients. Data on oculomotor and vestibular parameters were extracted and correlations with a range of clinical parameters were sought. Included studies (n = 17) reported on 185 patients. Abnormalities observed included the presence of saccadic intrusions (143/161) such as square-wave jerks (SWJ, 90/109) and ocular flutter (21/43), impaired eccentric gaze-holding (40/104), abnormal pursuit (81/93) and angular vestibulo-ocular reflex (aVOR) deficits (39/48). For visually-guided saccades (VGS), we frequently observed increases in saccade latency (27/38) and dysmetric saccades (71/93), whereas saccade velocity was more often preserved (37/43). Augmented anti-saccade (AS) latency, downbeat nystagmus and frequent macro-SWJ correlated with disease duration. Increased AS-latency and VGS-latency, frequent macro-SWJ, reduced aVOR-gain and augmented aVOR peak-latency correlated with disease severity. A broad range of oculomotor and vestibular deficits are documented in the literature. Impairments in pursuit, saccades and aVOR-responses are most commonly reported, and as such, should be prioritized as disease markers. Quantitative oculomotor testing in FRDA may facilitate early diagnosis and prove valuable in monitoring disease progression and treatment response.

Changes in saccadic intrusions over time as an objective biomarker to follow ALS disease progression

Objective: Saccadic Intrusions (SIs) are abnormal eye movements during gaze fixation. Studies have indicated the clinical relevance of SIs, especially of square wave jerks (SWJ) in ALS. We used a software-based platform to extract SIs as a part of an interventional drug trial. The objective was to examine SIs’ change over time as a potential biomarker of ALS disease progression. Methods: 28 ALS patients (61.95 ± 8.6 years) were assessed with the revised ALS Functional Rating Scale (ALSFRS-R) and with an oculometric test. Changes of SIs over time and correlations with ALSFRS-R and its bulbar subscale were calculated. A power calculation was conducted to understand the practical implications of results. Results: A significant increase of SWJ over trial duration was observed, with an increase in frequency (mean rise of 0.14 ± 0.28, p < 0.01), amplitude (0.001 ± 0.0016 degrees, p < 0.005), overall duration of SWJ (0.13 ± 0.25, in %, p < 0.01), and in their relative part out of all intrusions (0.18 ± 0.32, in %, p < 0.005). Negative correlations were found with the bulbar subscale (R=-0.43, −0.41, −0.39 and −0.47, respectively, p < 0.001). The required sample size for observing a 40% reduction in bulbar aspects when using the oculometric test (α = 0.05 and β = 0.8), was found to be 150 patients per arm, compared with 200 patients using the bulbar subscale. Conclusions: Evaluation of saccadic intrusions during fixation was able to detect disease progression over time, correlated with ALSFRS-R bulbar subscale. Eye movements can potentially serve as an objective biomarker in ALS clinical trials and reduce the required sample size to show clinical effect of therapies.

Immune‐mediated spastic ataxia masquerading as clinically probable multisystem atrophy in an elderly woman

AbstractBackgroundAutoimmune neurological syndromes pose diagnostic challenges due to their resemblance to neurodegenerative conditions. Autoimmune spastic ataxia is a rare phenomenon. This case presents a 56‐y‐old woman with subacute‐onset spastic ataxia, highlighting the complexities in diagnosis and the role of autoimmunity in such cases.Case PresentationA woman in her fifties developed progressive spastic ataxia over a year and presented to our outpatient department for evaluation. The patient exhibited clinical signs including saccadic intrusions, gaze‐evoked nystagmus, mixed dysarthria, spasticity, exaggerated reflexes, and cerebellar dysfunction. Brain magnetic resonance imaging (MRI) displayed the “hot cross bun sign” and cerebral and cerebellar atrophy. Initial tests yielded minimal abnormalities, but a positive antinuclear antibody (ANA) emerged. The patient initially declined immunotherapy. Upon symptom progression, a repeat cerebrospinal fluid (CSF) analysis showed inflammatory changes and a whole‐body positron emission tomography (PET) scan indicated reduced uptake in the cerebellum and brainstem. Subsequent paraneoplastic antibody testing revealed an unspecified neuronal antibody targeting capillaries and arterioles. Treatment with steroids, plasmapheresis, and azathioprine led to sustained improvement, reducing spasticity, and enabling her to walk short distances.ConclusionsThis case emphasizes the diagnostic complexity of autoimmune neurological syndromes, particularly spastic ataxia. Autoimmune etiology should be considered even when neurodegenerative conditions seem likely. The presence of neuronal antibodies, inflammatory CSF, and response to immunotherapy underscores the role of autoimmunity in this case. Additionally, the “hot cross bun sign” may not always signify neurodegeneration, but can indicate immune‐mediated neural damage. Recognizing autoimmune involvement early offers therapeutic possibilities and highlights the need for a comprehensive diagnostic approach in such cases.

Videoocular assessment of eye movement activity in an ataxia-telangiectasia: a case study.

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by progressive neurological deficits, including prominent oculomotor dysfunction. We report 5 cases of eye movement assessment in children 9-15years old with A-T. Three different oculomotor tasks (gaze holding, visually guided saccades and visual search) were used, and video-oculography was performed. Additionally, the scale for the assessment and rating of ataxia(SARA) score was used to assess severity of the cerebellar ataxia. Unstable gaze holding, nystagmus and saccadic intrusions were found. In addition to psychophysiological assessment results, we provide quantitative analysis of oculomotor activity, revealing a specific abnormal oculomotor pattern, consisting of (i) marked saccade hypermetria, (ii) unstable gaze holding, and (iii) gaze-evoked nystagmus. Our study opens the prospect to evaluate efficacy and safety of alternative methods for supporting the patient and improving his/her life quality.

Clinical utility of square-wave jerks in neurology and psychiatry.

Human eye fixation is steadily interrupted by small, physiological or abnormal, eye movements. Square-wave jerks (SWJ) are the most common saccadic intrusion which can be readily seen at the bedside and also quantified using oculographic techniques. Various neurological, neuropsychiatric and psychiatric disorders display abnormal fixational eye movement patterns characterized by frequent SWJ. For the clinician, SWJ are particularly important because they can be readily observed at the bedside. Here, we will discuss the pathological conditions that present with SWJ and explore the expanding body of literature suggesting that SWJ may serve as a potential indicator for various clinical conditions.

Usefulness of eye tracking systems in multiple sclerosis

Multiple sclerosis (MS) is a chronic disease of the central nervous system characterized by inflammation and neurodegeneration. It represents the leading cause of nontraumatic disability in young adults in many places around the world.Currently, for the objective quantification of the damage of the visual pathway swept‐source OCT (SS‐OCT) is considered the most appropriate technique. Additionally, during the course of the disease multiple neurological deficiencies can appear, including eye motility disorders.Patients may develop various ocular motor disorders (OMDs) affecting visual function and significantly increasing disability. These alterations involve visual function and may decrease quality of life perceived by patients because they affect, among other functions, reading capability.OMDs, can be analysed by several recording systems, although they have not been incorporated into the practice routine clinic due to its complexity, high costs and also because the value of these alterations is probably not known.It is possible that an accurate examination of motility eye, may have a substantial impact on the diagnosis and management of those patients. OMDs has been suggested as potential biomarker of early neurological deterioration and its evaluation could contribute to obtaining progression and response to treatments, facilitating translational development of so‐called precision medicine.Eye trackers are state‐of‐the‐art tools that can obtain valuable information of OMDs in neurological degenerations. In MS, oculomotor alterations as saccadic dysmetria, saccadic intrusions, nystagmus, fixational deficits, smooth pursuit impairment, skew deviation, optokinetic and vestibulo‐ocular reflex impairments, may go unnoticed because systematic examination of the oculomotor systems do not use routinely these techniques.As mentioned, objective recordings of eye movements through eye‐tracking systems are not currently performed widely, despite that they have been described as an important adjunct in diagnosis, documentation, and management of different neurologic conditions.In addition, eye tracking is also a capable method to investigate the relationship between behaviour and neural mechanisms. Eye motion recordings provide a measure of functional preservation of the nervous system, which should be recognized to be of significant importance in assessing a disease in which disability is manifested by disruption of normal neuronal functions.In fact, it has been described that eye tracking tasks (especially saccadic tasks) are often used as an adjunct to traditional scales for cognitive assessment. In addition, eye tracking data confirmed that MS is characterized by attention deficits.In conclusion, there is a growing interest in the use of eye tracking systems as biomarkers for MS. Specifically in this work we have analysed a large series MS patients to detect if any of the anomalies that patients refer to, such as reading difficulties, are related to disorders of the ocular motor systems.

Scale for Ocular Motor Disorders in Ataxia (SODA) in Patients with Multiple System Atrophy.

A clinical scale fully dedicated to evaluating ocular motor abnormalities is required for now. We investigated the utility of a recently developed Scale for Ocular motor Disorders in Ataxia (SODA) in patients with multiple system atrophy (MSA). We prospectively assessed SODA in consecutive patients with MSA between August 2021 and August 2023 at the Korea University Medical Center. The results of the clinical exam-based SODA were compared with those measured using video-oculography (VOG-guided SODA). We also compared the findings with other established clinical scales targeting patients with MSA, including the Unified Multiple System Atrophy Rating Scale (UMSARS) I-II, Movement Disorder Society-Unified Parkinson's Disease Rating Scale motor part (UPDRS-III), Scale for Assessment of Rating of Ataxia (SARA), Composite Autonomic Symptom Score-31 (COMPASS-31), and Composite Autonomic Severity Score (CASS). Twenty patients were enrolled in our study (17 with cerebellar-type MSA and three with Parkinson-type MSA). Scores ranged from 1 to 14 (median [interquartile range (IQR)] = 8 [5-10]). Among the subscales, saccades had a median score of 2.5 (IQR = 1-3), followed by ocular pursuit (1 [0-1]), nystagmus (1 [0-2]), saccadic intrusions (1 [0-1]), vestibulo-ocular reflex (VOR) (0.5 [0-1]), ocular alignment (0 [0-1]), and VOR cancellation (1 [0-1]). The clinical-exam-based SODA (p = 0.020) and VOG-guided SODA (p = 0.034) positively correlated with disease duration. No correlation was found between clinical exam-based SODA and other scales. Skew deviation, gaze-evoked nystagmus, VOR cancellation, and smooth pursuit had the highest precision among the items. Ocular misalignment and spontaneous and positional nystagmus were frequently false positive and were poorly detected with clinical exam-based SODA. Six patients with repeated evaluation exhibited higher scores, along with deterioration documented on other clinical scales. The SODA can reliably predict neurodegeneration as an additional clinical surrogate in MSA.

Opsoclonus and ocular flutter: evaluation and management.

Opsoclonus and ocular flutter are saccadic intrusions characterized by spontaneous, back-to-back, fast eye movements (saccades) that oscillate about the midline of central visual fixation without intervening inter-saccadic intervals. When this type of movement occurs exclusively in the horizontal plane, it is called ocular flutter. When it occurs in multiple planes (i.e. horizontal, vertical, and torsional) it is called opsoclonus. The most common etiologic categories are parainfectious and paraneoplastic diseases. Less common are toxic-metabolic, traumatic, or idiopathic origins. The mechanism of these movements relates to dysfunction of brainstem and cerebellar machinery involved in the generation of saccades. In this review, we discuss the characteristics of opsoclonus and ocular flutter, describe approaches to clinical evaluation and management of the patient with opsoclonus and ocular flutter, and review approaches to therapeutic intervention. Recent publications demonstrated eye position-dependent opsoclonus present only in left gaze, which may be related to dysfunction of frontal eye fields or structures in the cerebellar vermis. Opsoclonus and ocular flutter originate from a broad array of neuropathologies and have value from both a neuroanatomic and etiologic perspective.

Recording and interpretation of ocular movements: spontaneous and induced nystagmus

The ultimate purpose of eye movement is to maintain clear vision by ensuring that images of observed objects are focused on the fovea in the retina. Accurate evaluation of ocular movements, including nystagmus and saccadic intrusions, provides very useful information for determining the overall function and abnormality of the complex oculomotor system, from the peripheral vestibular system to the cerebrum. Eye movement tests are therefore essential for the accurate diagnosis of patients who complain of dizziness and imbalance. They help to predict lesion locations from the peripheral vestibular system to the central cerebral cortex and play an important role in differentiation from other diseases. The methodology of recording and interpreting ocular movements using video-oculography are described in this review article.

Eye movement study in essential tremor patients and its clinical correlates.

Essential tremor (ET) encompasses a wide spectrum of motor and non-motor features. Eye movement abnormalities were first reported two decades ago as an atypical finding in ET. Today, a growing number of publications about eye movement abnormalities in neurodegenerative diseases have helped understand their pathophysiology and the basis of their phenotypic variability. Thus, addressing such aspect in ET may disentangle, based on the oculomotor network abnormalities, the dysfunctional brain pathways in ET. In this study, we aimed to describe neurophysiological eye movement abnormalities in ET and their clinical correlates in terms of cognition and other associated clinical signs. We conducted a cross-sectional study in a tertiary neurology referral center including consecutive ET patients and cognitively normal healthy controls (HC) matched for age and sex. The study protocol included the assessment of voluntary horizontal saccades, smooth pursuit, anti-saccades and saccadic intrusions. We assessed the associated motor signs, cognitive functions and the presence of rapid eye movement disorder (RBD). Sixty-two ET patients and 66 HC were enrolled in the study. Eye movement examination showed significant abnormalities in comparison with HC (46.7% vs 20%, p = 0.002). Prolonged saccadic latency (38.7%, p = 0.033) and altered smooth pursuit (38.7%, p = 0.033) were the most common abnormalities in ET patients. Anti-saccadic errors (16% vs 0% in HC, p = 0.034) correlated with the presence of rigidity (p = 0.046), bradykinesia (p = 0.001), cognitive dysfunction (p = 0.006), executive dysfunction (p = 0.0002), apraxia (p = 0.0001), altered verbal fluency (p = 0.013) and altered backward digit span (p = 0.045) along with the presence of RBD (p = 0.035). Square-wave jerks (11.5% vs 0% in HC, p = 0.0024) correlated with rest tremor. A distinctive phenotype of ET could emerge out of this study characterized by anti-saccadic errors and a sub-cortical cognitive profile, consecutive to the disruption of the cerebello-thalamo-cortical loop. Patients with anti-saccadic errors could be cognitively vulnerable and in need of a close monitoring of their cognitive efficiency during the disease's progression. They may as well convert to Parkinson disease if they present with parkinsonism, RBD and square-wave jerks and require, consequently, a close observation of their motor progression.

Quantitative Oculomotor Assessment in Hereditary Ataxia: Discriminatory Power, Correlation with Severity Measures, and Recommended Parameters for Specific Genotypes

Characterizing bedside oculomotor deficits is a critical factor in defining the clinical presentation of hereditary ataxias. Quantitative assessments are increasingly available and have significant advantages, including comparability over time, reduced examiner dependency, and sensitivity to subtle changes. To delineate the potential of quantitative oculomotor assessments as digital-motor outcome measures for clinical trials in ataxia, we searched MEDLINE for articles reporting on quantitative eye movement recordings in genetically confirmed or suspected hereditary ataxias, asking which paradigms are most promising for capturing disease progression and treatment response. Eighty-nine manuscripts identified reported on 1541 patients, including spinocerebellar ataxias (SCA2, n = 421), SCA3 (n = 268), SCA6 (n = 117), other SCAs (n = 97), Friedreich ataxia (FRDA, n = 178), Niemann-Pick disease type C (NPC, n = 57), and ataxia-telangiectasia (n = 85) as largest cohorts. Whereas most studies reported discriminatory power of oculomotor assessments in diagnostics, few explored their value for monitoring genotype-specific disease progression (n = 2; SCA2) or treatment response (n = 8; SCA2, FRDA, NPC, ataxia-telangiectasia, episodic-ataxia 4). Oculomotor parameters correlated with disease severity measures including clinical scores (n = 18 studies (SARA: n = 9)), chronological measures (e.g., age, disease duration, time-to-symptom onset; n = 17), genetic stratification (n = 9), and imaging measures of atrophy (n = 5). Recurrent correlations across many ataxias (SCA2/3/17, FRDA, NPC) suggest saccadic eye movements as potentially generic quantitative oculomotor outcome. Recommendation of other paradigms was limited by the scarcity of cross-validating correlations, except saccadic intrusions (FRDA), pursuit eye movements (SCA17), and quantitative head-impulse testing (SCA3/6). This work aids in understanding the current knowledge of quantitative oculomotor parameters in hereditary ataxias, and identifies gaps for validation as potential trial outcome measures in specific ataxia genotypes.

An improved algorithm for saccadic intrusion qualification under air traffic control situation

Saccadic intrusions are saccadic deviations that interrupt fixations. Saccadic intrusions have the unique characteristics of regular saccades and a small amplitude and round trip, providing a foundation for accurately identifying and quantifying saccadic intrusions. However, currently, rapid and accurate identification algorithms for saccadic intrusions of air traffic controllers are lacking. This study aimed to improve Tokuda's quantification algorithm for saccadic eye movement deviation in terms of data preprocessing, saccadic eye movement identification, and saccade amplitude threshold. The eye movement data were recorded using an eye tracker at a frequency of 100 Hz and obtained from the control simulation experiment. A total of 20 participants with basic control knowledge participated in this study, and finally 54 sets of data were obtained. The analysis of eye movement data showed that the saccadic intrusion quantification value of 36 of 54 sets of data obtained by the improved algorithm was closer to the value output by the manual identification method compared with the original algorithm. The results showed that these improvements had positive effects on the algorithm.

Ocular myasthenia gravis saccades as a measure of extraocular muscle function.

It is important to understand the pathophysiology of ocular myasthenia gravis (OMG) to improve treatment. To use modern video-oculography to characterise saccadic eye movements in patients with OMG, including anti-AChR, anti-MuSK, anti-LRP4, and seronegative OMG. In total, 21 patients with OMG and five age-matched healthy control subjects underwent video-oculography. Participants performed a sequence of horizontal saccades (3 minutes each) at ±5°, ± 10°, and ±20°, followed by 3 minutes of saccades directed at randomly presented targets at ±5°, ± 10°, and ±15°. We recorded the direction, amplitude, duration, peak, and average velocity of each saccade for each task for each participant. Saccadic amplitude, duration, and average velocity were all lower in OMG patients than in control subjects (p<0.021). Saccadic amplitude and velocity decreased over time, but this decrease was similar in OMG patients and control subjects. Fixation drift and ocular disparity tended to be greater in OMG patients than in control subjects. Saccadic intrusions occurred more frequently in OMG patients than in control subjects (p<0.001). No significant effects of time or group by time on fixation drift or ocular disparity were found. Saccadic velocities in OMG patients differed from those in normal control subjects, which suggests that OMG affects fast-twitch fibres, although fast-twitch fibres were still able to generate "twitch" or "quiver" movements in the presence of even severe ophthalmoplegia. Slow-twitch muscle fibres involved in gaze holding were also affected, accounting for increased fixation drift following saccades. Our objective finding of increased fixation drift and a larger number of saccadic intrusions mirror our anecdotal experience of patients with OMG who report significant diplopia despite minimal ophthalmoplegia on examination. Such microsaccades may be a surrogate for compensation of a gaze-holding deficit in MG.

Eye movements and eating disorders: protocol for an exploratory experimental study examining the relationship in young-adult women with subclinical symptomatology

BackgroundRecent research indicates that patients with anorexia (AN) show specific eye movement abnormalities such as shorter prosaccade latencies, more saccade inhibition errors, and increased rate of saccadic intrusions compared to participants without AN. However, it remains unknown whether these abnormal eye movement patterns, which may serve as potential biomarkers and endophenotypes for an early diagnosis and preventive clinical treatments, start to manifest also in people with subclinical eating disorders (ED) symptomatology. Therefore, we propose a protocol for an exploratory experimental study to investigate whether participants with subclinical ED symptomatology and control participants differ in their performance on several eye movement tasks.MethodsThe sample will be recruited through convenience sampling. The Eating Disorder Examination Questionnaire will be administered as a screening tool to split the sample into participants with subclinical ED symptomatology and control participants. A fixation task, prosaccade/antisaccade task, and memory-guided task will be administered to both groups. Additionally, we will measure anxiety and premorbid intelligence as confounding variables. Means comparison, exploratory Pearson's correlations and discriminant analysis will be performed.DiscussionThis study will be the first to elucidate the presence of specific eye movement abnormalities in participants with subclinical ED symptomatology. The results may open opportunities for developing novel diagnostic tools/therapies being helpful to the EDs research community and allied fields.

Immature brain structures were associated with poorer eye movement performance at 8years of age in preterm born children.

Eye movements have rarely been explored in preterm born children. The aim of this study was to compare horizontal eye movements in children born preterm and full term when they reached 8years of age. Eye movements were recorded in 24 preterm born children (18 boys) and 26matched controls (19 boys), recruited by a French hospital, using an eye tracker. This identified different types of visually guided saccades, namely step, gap, overlap and antisaccades and pursuit eye movements. The saccades task measured the latency and the percentage of anticipatory and express saccades and errors. The pursuit task measured the gain and percentage of intrusive saccades. This study confirmed that children born at 24-28weeks of gestation demonstrated a global deficit in inhibitory processes compared to children born full term. The saccades were less precise in the preterm group, anticipatory and express saccades were elevated and there was a high occurrence of intrusive saccades during pursuit movements. These findings suggest that preterm born children have immature brain structures, particularly the parietal and frontal cortexes that are responsible for both saccade and pursuit performance. These could have been the cause of the abnormal inhibitory control measured in this study.

Unusual Presentation of PLA2G6-Related Neurodegeneration with Retinal Vasculitis.

Unusual Presentation of PLA2G6-Related Neurodegeneration with Retinal Vasculitis.

Medical Treatment of Nonvascular Central Vertigo

Central vertigo is the common symptom resulting from abnormalities in the central nervous system, caused by various diseases, which include neurodegenerative, vascular, inflammation, infection, tumor, paraneoplastic, toxic, or metabolic disorders. Since the treatment of central vertigo depends on the causes, an accurate diagnosis should be preceded the treatment through a detailed neurotologic examination and laboratory evaluation. Also, it is important to identify and document the neurologic findings accompanied by central vertigo, because some medication focuses on the ocular motor abnormalities as nystagmus or saccadic intrusion. Here, we will review the medical treatment for central vertigo.

FV 3. Diagnostic value of oculomotor parameters in progressive supranuclear palsy: a monocentric study in 100 patients

Introduction. For progressive supranuclear palsy (PSP), oculomotor function is one of the core features on which the diagnosis is based upon according to the diagnostic criteria by the Movement Disorder Society (MDS) supported PSP-Study-Group from 2017 (“O criterion”). The aim of this study was to analyze the value of specific oculomotor parameters. Material/Method. An analysis of the videooculographic examinations of smooth pursuit eye movements and visually guided reactive saccades in 100 PSP patients and 49 matched control subjects was performed. Group differences as well as correlations were tested at a two-sided level α=0.05. Cut-off values for the development of new subgroups were defined by the fifth or 95th percentile of specific parameters of the control group. ROC-analyses were used to determine sensitivity and specificity. Results. Each of the investigated oculomotor parameters (for smooth pursuit eye movements gain, for saccades latency, gain, peak eye velocity, asymmetry of velocities up- and downwards, rate of saccadic intrusions (SI)) was significantly altered in PSP compared with the control population (p<0.0001 each). The threshold for vertical saccade velocity was approximately 240°/s for both components so that about 70% of the patients could be captured. A cut-off value of 9.60°/s was determined for SI, and approximately 56% of the patients achieved higher values. By combining both parameters, almost 80% of the patients could be classified. With regard to the specifically calculated asymmetry of the vertical saccade velocities, 34% of the patients were abnormal at a threshold of 0.42 (overview in Fig. 1). The majority of patients (63.5%) performed faster downward than upward saccades. The vertical saccade velocity and SI had a high specificity of more than 95%, while sensitivity was maximally 60% for the velocity components and 54.2% for the SI. At similar specificity, the asymmetry reached a sensitivity of 27.1%. Discussion. The results for vertical saccade velocity and SI, respectively, emphasized their relevance as part of the MDS-PSP diagnostic criteria, whereas the significance of the asymmetry of the vertical velocities was limited. With respect to directional tendency, the findings are still heterogeneous. In future evaluations, unbiased quantifications of clinical parameters offer a good possibility to further develop the quality of the diagnostic procedures used for PSP. Fig. 1.

Gaze-holding and anti-GAD antibody: prototypic heterogeneous motor dysfunction in immune disease.

The variability in motor dysfunction is not uncommon in autoimmune disorders. Antibody-mediated system-wide malfunction or effects on the neural network shared by two independent pathophysiological processes can cause such heterogeneity. We tested this prediction for motor dysfunction during gaze holding in 11 patients with increased titers of glutamic acid decarboxylase (anti-GAD) antibody. High-resolution oculography measured horizontal and vertical eye positions. The analysis was performed with customized signal processing algorithms. Downbeat and gaze-evoked nystagmus commonly coexisted; one patient had a combination of upbeat and gaze-evoked nystagmus. The nystagmus was associated with saccadic intrusions in 10 patients; all had squarewaves, but five also had saccadic oscillations. The nystagmus and saccadic intrusions, both in the same axis of eye rotations, were not uncommon. Tandem appearance of the episodes of nystagmus and saccadic intrusions suggested a coupling between the two abnormalities. We speculated a unifying framework where the anti-GAD antibody inhibited (GAD mediated) conversion of glutamate to gamma-aminobutyric acid (GABA). Paucity GABA and excess of glutamate cause nystagmus (less GABA) and high-frequency saccadic oscillations (excessive glutamate).

Opsoclonus-myoclonus-ataxia syndrome in children.

Opsoclonus-myoclonus-ataxia syndrome is a rare neuroimmunologic disorder typically presenting in previously healthy infants and toddlers. It is characterized by a clinical triad of (1) erratic saccadic intrusions; (2) myoclonus and/or ataxia; (3) behavioral features, typified by developmental plateauing, irritability and insomnia. About half of cases are associated with an underlying neuroblastoma and diagnostic imaging is essential once OMAS is suspected. A thorough workup, including serum, urine, and cerebrospinal fluid studies is critical to identify underlying biomarkers of OMAS itself or neuroblastoma. Historically, many children had relatively poor long-term outcomes, with residual neurologic and/or neuropsychiatry sequelae typical. More recent concepts have emphasized combined immunotherapy regimens that offer hope for better outcomes in children with this remarkable, challenging disease.