Characteristic eye movements in ataxia-telangiectasia-like disorder: An explanatory hypothesis

Objective: To investigate cerebellar dysfunctions and quantitatively characterize specific oculomotor changes in ataxia-telangiectasia-like disorder (ATLD), a rare autosomal recessive disease caused by mutations in the MRE11 gene. Additionally, to further elucidate the pathophysiology of cerebellar damage in the ataxia-telangiectasia (AT) spectrum disorders. Methods: Saccade dynamics, metrics, and visual fixation deficits were investigated in two Italian adult siblings with genetically confirmed ATLD. Visually guided saccades were compared with those of 40 healthy subjects. Steady fixation was tested in primary and eccentric positions. Quantitative characterization of saccade parameters, saccadic intrusions (SI), and nystagmus was performed. Results: Patients showed abnormally hypermetric and fast horizontal saccades to the left and greater inaccuracy than healthy subjects in all saccadic eye movements. Eye movement abnormalities included slow eye movements that preceded the initial saccade. Horizontal and vertical spontaneous jerk nystagmus, gaze-evoked, and rebound nystagmus were evident. Fixation was interrupted by large square-wave jerk SI and macrosaccadic oscillations. Conclusion: Slow eye movements accompanying saccades, SI, and cerebellar nystagmus are frequently seen in AT patients, additionally our ATLD patients showed the presence of fast and hypermetric saccades suggesting damage of granule cell-parallel fiber-Purkinje cell synapses of the cerebellar vermis. A dual pathogenetic mechanism involving neurodevelopmental and neurodegenerative changes is hypothesized to explain the peculiar phenotype of this disease

Pseudoacromegaly

© 2018 Elsevier Inc. Individuals with acromegaloid physical appearance or tall stature may be referred to endocrinologists to exclude growth hormone (GH) excess. While some of these subjects could be healthy individuals with normal variants of growth or physical traits, others will have acromegaly or pituitary gigantism, which are, in general, straightforward diagnoses upon assessment of the GH/IGF-1 axis. However, some patients with physical features resembling acromegaly – usually affecting the face and extremities –, or gigantism – accelerated growth/tall stature – will have no abnormalities in the GH axis. This scenario is termed pseudoacromegaly, and its correct diagnosis can be challenging due to the rarity and variability of these conditions, as well as due to significant overlap in their characteristics. In this review we aim to provide a comprehensive overview of pseudoacromegaly conditions, highlighting their similarities and differences with acromegaly and pituitary gigantism, to aid physicians with the diagnosis of patients with pseudoacromegaly.PM is supported by a clinical fellowship by Barts and the London Charity. Our studies on pituitary adenomas and related conditions received support from the Medical Research Council, Rosetrees Trust and the Wellcome Trust

A GABAergic Dysfunction in the Olivary–Cerebellar–Brainstem Network May Cause Eye Oscillations and Body Tremor. II. Model Simulations of Saccadic Eye Oscillations

Eye and body oscillations are shared features of several neurological diseases, yet their pathophysiology remains unclear. Recently, we published a report on two tennis players with a novel presentation of eye and body oscillations following self-administration of performance-enhancing substances. Opsoclonus/flutter and limb tremor were diagnosed in both patients. Common causes of opsoclonus/flutter were excluded. High-resolution eye movement recordings from one patient showed novel spindle-shaped, asymmetric saccadic oscillations (at ~3.6 Hz) and ocular tremor (~40–60 Hz). Based on these findings, we proposed that the oscillations are the result of increased GABAA receptor sensitivity in a circuit involving the cerebellum (vermis and fastigial nuclei), the inferior olives, and the brainstem saccade premotor neurons (excitatory and inhibitory burst neurons, and omnipause neurons). We present a mathematical model of the saccadic system, showing that the proposed dysfunction in the network can reproduce the types of saccadic oscillations seen in these patients

Eye Movements in Parkinson’s Disease and Inherited Parkinsonian Syndromes

Despite extensive research, the functions of the basal ganglia (BG) in movement control have not been fully understood. Eye movements, particularly saccades, are convenient indicators of BG function. Here, we review the main oculomotor findings reported in Parkinson’s disease (PD) and genetic parkinsonian syndromes. PD is a progressive, neurodegenerative disorder caused by dopaminergic cell loss within the substantia nigra pars compacta, resulting in depletion of striatal dopamine and subsequent increased inhibitory BG output from the internal globus pallidus and the substantia nigra pars reticulata. Eye movement abnormalities are common in PD: anomalies are more evident in voluntary than reflexive saccades in the initial stages, but visually guided saccades may also be involved at later stages. Saccadic hypometria (including abnormally fragmented saccades), reduced accuracy, and increased latency are among the most prominent deficits. PD patients show also unusually frequent and large square wave jerks and impaired inhibition of reflexive saccades when voluntary mirror saccades are required. Poor convergence ability and altered pursuit are common. Inherited parkinsonisms are a heterogeneous group of rare syndromes due to gene mutations causing symptoms resembling those of PD. Eye movement characteristics of some parkinsonisms have been studied. While sharing some PD features, each syndrome has a distinctive profile that could contribute to better define the clinical phenotype of parkinsonian disorders. Moreover, because the pathogenesis and the underlying neural circuit failure of inherited parkinsonisms are often well defined, they might offer a better prospect than idiopathic PD to understand the BG function

Eight and a Half Syndrome with Hemiparesis and Hemihypesthesia: The Nine Syndrome?

5no"Eight-and-a-half" syndrome is "one-and-a-half" syndrome (conjugated horizontal gaze palsy and internuclear ophthalmoplegia) plus ipsilateral fascicular cranial nerve seventh palsy. This rare condition, particularly when isolated, is caused by circumscribed lesions of the pontine tegmentum involving the abducens nucleus, the ipsilateral medial longitudinal fasciculus, and the adjacent facial colliculus. Its recognition is therefore of considerable diagnostic value. We report a 71-year-old man who presented with eight and a half syndrome associated with contralateral hemiparesis and hemihypesthesia, in which brain magnetic resonance imaging scans revealed a lacunar pontine infarction also involving the corticospinal tract and medial lemniscus. These features could widen the spectrum of pontine infarctions, configuring a possible "nine" syndromereservedmixedRosini F;Pretegiani E;Guideri F;Cerase A;Rufa ARosini, Francesca; Pretegiani, Elena; Guideri, Francesca; Cerase, A; Rufa, Alessandr

Eye movement recording and nonlinear dynamics analysis - The case of saccades

5siEvidence of a chaotic behavioral trend in eye movement dynamics was examined in the case of a saccadic temporal series collected from a healthy human subject. Saccades are highvelocity eye movements of very short duration, their recording being relatively accessible, so that the resulting data series could be studied computationally for understanding the neural processing in a motor system. The aim of this study was to assess the complexity degree in the eye movement dynamics. To do this we analyzed the saccadic temporal series recorded with an infrared camera eye tracker from a healthy human subject in a special experimental arrangement which provides continuous records of eye position, both saccades (eye shifting movements) and fixations (focusing over regions of interest, with rapid, small fluctuations). The semi-quantitative approach used in this paper in studying the eye functioning from the viewpoint of non-linear dynamics was accomplished by some computational tests (power spectrum, portrait in the state space and its fractal dimension, Hurst exponent and largest Lyapunov exponent) derived from chaos theory. A high complexity dynamical trend was found. Lyapunov largest exponent test suggested bi-stability of cellular membrane resting potential during saccadic experiment.openopenAştefănoaei, Corina; Pretegiani, Elena; Optican, L. M; Creangă, Dorina; Rufa, AlessandraAştefănoaei, Corina; Pretegiani, Elena; Optican, L. M; Creangă, Dorina; Rufa, Alessandr

Neuromyotonia as paraneoplastic manifestation of bladder carcinoma.

Neuromyotonia(NMT) or Isaacs syndrome is a rare syndrome characterized by continuous spontaneous muscle fiber contraction resulting from hyperexcitability of peripheral nerves often associated with autoimmune disorders and tumours. Here we report an unpublished association of NMT and bladder canc