Understanding Parinaud’s Syndrome

Parinaud’s syndrome involves dysfunction of the structures of the dorsal midbrain. We investigated the pathophysiology related to the signs and symptoms to better understand the symptoms of Parinaud’s syndrome: diplopia, blurred vision, visual field defects, ptosis, squint, and ataxia, and Parinaud’s main signs of upward gaze paralysis, upper eyelid retraction, convergence retraction nystagmus (CRN), and pseudo-Argyll Robertson pupils. In upward gaze palsy, three structures are disrupted: the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF), interstitial nucleus of Cajal (iNC), and the posterior commissure. In CRN, there is a continuous discharge of the medial rectus muscle because of the lack of inhibition of supranuclear fibers. In Collier’s sign, the posterior commissure and the iNC are mainly involved. In the vicinity of the iNC, there are two essential groups of cells, the M-group cells and central caudal nuclear (CCN) group cells, which are important for vertical gaze, and eyelid control. Overstimulation of the M group of cells and increased firing rate of the CCN group causing eyelid retraction. External compression of the posterior commissure, and pretectal area causes pseudo-Argyll Robertson pupils. Pseudo-Argyll Robertson pupils constrict to accommodation and have a slight response to light (miosis) as opposed to Argyll Robertson pupils were there is no response to a light stimulus. In Parinaud’s syndrome patients conserve a slight response to light because an additional pathway to a pupillary light response that involves attention to a conscious bright/dark stimulus. Diplopia is mainly due to involvement of the trochlear nerve (IVth cranial nerve. Blurry vision is related to accommodation problems, while the visual field defects are a consequence of chronic papilledema that causes optic neuropathy. Ptosis in Parinaud’s syndrome is caused by damage to the oculomotor nerve, mainly the levator palpebrae portion. We did not find a reasonable explanation for squint. Finally, ataxia is caused by compression of the superior cerebellar peduncle.

Distinct purinergic receptor-mediated currents of rat oculomotor integrator neurons characterized by different firing patterns

The roles of purinergic signaling on vertical (mediated by the interstitial nucleus of Cajal; INC) and horizontal (prepositus hypoglossal nucleus; PHN) gaze control are not understood. Here, we report three current types induced by ATP in INC neurons; the distribution of these current types across different types of INC neurons is different from that in PHN neurons. These results suggest distinct modes of purinergic modulation in horizontal and vertical gaze control centers.

Current-dependent Ocular Tilt Reaction in STN-DBS: evidence for a putative incerto-interstitial pathway?

Objective: To report a patient with Parkinson’s disease presenting with a combined vestibular, oculomotor and postural syndrome dependent of deep brain stimulation (DBS) of the subthalamic nucleus. Methods: In a systematic monopolar review, eye, head and trunk position in roll and pitch plane were documented as a function of stimulation amplitude and field direction. Repeat ocular coherence tomography was used to estimate ocular torsion. The interstitial nucleus of Cajal (INC), zona incerta (ZI) and ascending vestibular fiber tracts were segmented on MRI using both individual and normative structural and connectomic data. Thresholded symptom-associated volumes of tissue activated (VTA) were calculated based on documented stimulation parameters. Results: Ipsilateral ocular tilt reaction and body lateropulsion as well as contralateral torsional nystagmus were elicited by the right electrode in a current-dependent manner and subsided after DBS deactivation. With increasing currents, binocular tonic upgaze and subsequently body retropulsion could be elicited, consistent with an irritative effect on the Interstitial Nucleus of Cajal (INC). Symptom-associated VTA was found to overlap with the dorsal zona incerta (dZI) and the lateral ipsilateral vestibulothalamic tract (IVTT), while lying in close proximity to the medial IVTT and rather distant to the INC proper. As described in non-human primates, a ZI-to-INC, “incerto-interstitial” tract (IIT) with contact to the medial-uppermost portion of the VTA could be traced. By ways of directional current steering laterally to both tracts, therapeutic response could be preserved while vestibular side effects were minimized. Conclusion: Unilateral stimulation of mesencephalic vestibular-related circuitry induces an ipsilateral vestibular, oculomotor and postural roll-plane syndrome, which converts into a combined pitch-plane syndrome, when functional activation expands to the bilateral INC. The phenomenology of the roll-plane syndrome in this patient points to an activation of INC neurons by DBS, hypothetically via a potentially aberrant incerto-interstitial pathway. Directional current steering proved useful in managing this rare side effect.

Unraveling the mysteries of the midbrain – A case report

Context: The rostral midbrain and thalamomesencephalic junction are the supranuclear premotor control of vertical eye movements, and is supplied by the posterior thalamo-subthalamic paramedian artery originated from P1 segment of posterior cerebral artery. Case report: A 51-year-old man presented with sudden speech difficulties, dizziness and dyplopia, associated with moderate intensity headache. Neuroophthalmological examination revealed incomplete ptosis of the right eye, with mydriatic pupil, poorly reactive to light. No eye movements were present on attempted upward gaze. On attempted downward gaze, depression of the left eye was observed but with absent saccades. Lateral gaze to the right was intact, while attempted gaze deviation to the left revealed adduction deficit of the right eye with incomplete abduction of the left eye without nystagmus. Convergence was absent. He exhibited left hemiataxia with left hypoestesia. MRI showed acute right paramedian thalamic and mesencephalic stroke. Conclusions: About the vertical one and a half syndrome, it was suggested damage in the pathway to contralateral downgaze neurons before its decussation with the unilateral interstitial nucleus of Cajal. As for the contralateral lateral rectus palsy we infer that this patient’s abduction deficit was due to pseudo-abducens palsy, with several mechanisms that could explain abduction deficits associated with upgaze palsy. Claude’s syndrome is usually explained by a lesion of oculomotor nerve fascicle and the superior cerebellar peduncle, affecting cerebellothalamic connections.

Three-Dimensional Identification of the Medial Longitudinal Fasciculus in the Human Brain: A Diffusion Tensor Imaging Study

Background: The medial longitudinal fasciculus (MLF) interacts with eye movement control circuits involved in the adjustment of horizontal, vertical, and torsional eye movements. In this study, we attempted to identify and investigate the anatomical characteristics of the MLF in human brain, using probabilistic diffusion tensor imaging (DTI) tractography. Methods: We recruited 31 normal healthy adults and used a 1.5-T scanner for DTI. To reconstruct MLFs, a seed region of interest (ROI) was placed on the interstitial nucleus of Cajal at the midbrain level. A target ROI was located on the MLF of the medulla in the reticular formation of the medulla. Mean values of fractional anisotropy, mean diffusivity, and tract volumes of MLFs were measured. Results: The component of the MLF originated from the midbrain MLF, descended through the posterior side of the medial lemniscus (ML) and terminated on the MLF of medulla on the posterior side of the ML in the medulla midline. DTI parameters of right and left MLFs were not significantly different. Conclusion: The tract of the MLF in healthy brain was identified by probabilistic DTI tractography. We believe this study will provide basic data and aid future comparative research on lesion or age-induced MLF changes.

Gaze Holding and the Neural Integrator

This chapter reviews the neural network that temporally integrates premotor, velocity-coded signals to achieve tonic contraction of the extraocular muscles to hold the eyes at an eccentric position in the orbits. The mechanical properties of the eye and its supporting tissues are quantified and related to the pulse-slide-step neural command for a saccadic change in eye position. The anatomical substrate and neuropharmacology of the neural integrator is reviewed, including nucleus prepositus hypoglossi, interstitial nucleus of Cajal and cerebellum. Mathematical and animal models for the neural integrator are discussed, addressing points about how a leaky or unstable integrator may arise. Clinical and laboratory evaluation of gaze holding is summarized. Effects of experimentally inactivating the neural integrator are compared with clinical disorders affecting gaze holding, including a discussion of the pathogenesis of gaze-evoked nystagmus and Alexander’s law. Compensatory mechanisms for a leaky neural integrator are discussed, including centripetal, rebound, and gaze-evoked nystagmus.

Disorders of Ocular Motility Due to Disease of the Brainstem, Cerebellum, and Diencephalon

This chapter reviews clinical features (with illustrative video cases) and pathophysiology of medullary lesions, including Wallenberg’s syndrome and oculopalatal tremor. Manifestations and pathophysiology of three cerebellar syndromes are described (flocculus and paraflocculus, nodulus and ventral uvula, dorsal vermis and fastigial nucleus), applying these principles to interpret the effects of developmental disorders (e.g., Chiari malformation), hereditary ataxia, paraneoplastic cerebellar degeneration, cerebellar stroke, and cerebellar tumors. Characteristics of pontine lesions are discussed, including lesions of the abducens nucleus, paramedian pontine reticular formation (PPRF), internuclear ophthalmoplegia (INO), one-and-a-half syndrome, slow horizontal saccades, and saccadic oscillations. The effects of midbrain lesions are summarized, including lesions affecting the rostral interstitial nucleus of the medial longitudinal fasciculus (RIMLF), interstitial nucleus of Cajal, posterior commissure, and more diffuse processes causing slow vertical saccades or vertical gaze palsy (dorsal midbrain syndrome), including Whipple’s disease. Effects of lesions affecting the superior colliculus, thalamus, and pulvinar are also discussed.

The Neural Basis for Conjugate Eye Movements

This chapter draws on a range of studies of macaque and humans to forge an anatomical scheme for the control of gaze. At each stage, this scheme is used to predict effects of focal lesions on the control of gaze, with video examples. Contributions include the abducens nucleus, medial longitudinal fasciculus (MLF), and paramedian pontine reticular formation (PPRF) to horizontal gaze; the rostral interstitial nucleus of the medial longitudinal fasciculus (RIMLF), interstitial nucleus of Cajal, and posterior commissure to vertical gaze; cerebellar flocculus, paraflocculus, dorsal vermis, fastigial nucleus, and inferior olive to adaptive optimization of gaze. Cortical control of gaze by structures including primary visual cortex (V1), middle temporal visual area (MT, V5), medial superior temporal visual area (MST), posterior parietal cortex, frontal eye fields, supplementary eye fields, dorsolateral prefrontal cortex, cingulate cortex, descending pathways, thalamus, pulvinar, caudate, substantia nigra pars reticulata, subthalamic nucleus, and superior colliculus are each discussed.