Convergence Insufficiency

Blepharoclonus; Convergence Insufficiency; Slow Hypometric Saccades in all directions of gaze; Saccadic Breakdown of Smooth PursuitDouble visionThe patient is a 73 year old man with a ten year history of idiopathic Parkinson's disease characterized by difficulty in walking, generalized rigidity and a mild tremor of his hands at rest with deterioration in his handwriting. He denied any memory impairment or loss of cognitive function. He was referred for a neuro-ophthalmic evaluation with an 18 month history of intermittent horizontal double vision (diplopia) and when watching television, he could see the images on the screen split apart into two. He was able to refocus a single image by transiently closing his eyes or blinking. For reading, he used glasses with a prism correction.This patient with idiopathic Parkinson's Disease (PD) shows: • Impaired convergence • Slow hypometric saccades in all directions of gaze • Saccadic substitution for smooth pursuit eye movements • Poor visual suppression of the vestibular ocular reflex • No square wave jerks • Decreased spontaneous blink rate • Blepharospasm to light shone in the eyes The patient also shows: • A rigidity of the neck with the head flexed and tilted to the right • A mild head tremor • Mask-like face • Slow (akinetic) head and neck movements Most patients with PD, like this patient, show only minor ocular motility abnormalities at the bedside that often cannot be differentiated from findings in healthy elderly subjects. (6,7) The standard method for testing convergence is to slowly bring the examiner's finger towards the patient's bridge of the nose. In this video, the patient is asked to converge the eyes to fix on a white headed pin held near to the eyes. Alternate cover test of the eyes fixating on a near target shows an exophoria, i.e. the covered eye moves from an exo deviated position inwards to take up fixation when the eye is uncovered. Three factors impair his ability to converge his eyes: 1) age, 2) Parkinson's disease, and 3) medications (Sinemet). Diplopia on reading can be corrected by the prescription of appropriate prism glasses. When the patient wears the prism glasses prescribed, repeating the alternate cover test over the glasses shows a reduction in the movement of the exo deviated eye to take up fixation or no movement at all. Slow saccades occur in a variety of diseases affecting the pons: Spinocerebellar ataxia (SCA), especially SCA2 Huntington's disease Progressive supranuclear palsy Lytico-Bodig disease Whipple's disease Wilson's disease and Some cases of Amyotrophic lateral sclerosis (3) PSP in the early stage is often clinically misdiagnosed as Parkinson's Disease (PD). These two disorders are distinguishable by several clinical features. In PSP a supranuclear gaze palsy is characteristic and at onset presents with an inability to voluntarily look down. Table 7-3 and Table 7-4 Mendez MF and Cummings JL Dementia A Clinical Apporach, 3rd Edition (4).Imaging studies are not available in this patient. In a normal elderly subject, MR of the midbrain is compared with the MR of a patient with PD. Figure 1: Axial T2WI through the midbrain shows the normal pars compacta, the space between the substantia nigra and red nuclei. Figure 2: Axial T2WI in a patient with PD shows the midbrain is atrophic and the red nuclei and substantia nigra almost touch each other because the pars compacta is greatly reduced. Courtesy Anne Osborn, M.D. PET studies using fluorodopa in PD patients reveal markedly diminished uptake in the putamen. MRI spectroscopy in PD patients without dementia shows non-specific temporoparietal cortical dysfunction.The basal ganglia consist of the striatum (caudate nucleus and putamen) and globus pallidus, plus two related nuclei, the subthalamic nucleus and the substantia nigra. The substantia nigra begins just below the subthalamic nucleus and runs the length of the midbrain on either side, dorsal to the cerebral peduncle. It consists of a densely cellular, heavily pigmented portion (the pars compacta or SNc) and a relatively hypocellular zone (the pars reticulata or SNr). There is no evidence for a specific nucleus for convergence, which was initially wrongly attributed to the nucleus of Perlia, and disputed by Warwick and Buttner-Ennever and Akert. Anatomical studies have shown that a band of scattered cells just dorsal and dorsolateral to the oculomotor nucleus called subgroup C by Buttner-Ennever and Akert provide the neuronal substrate for the premotor control of vergence. (1,2) Excitatory inputs to the C-group result in vergence movements with a downward component.(5) It is unclear how the vergence signals are transmitted to the abducens nucleus.An autopsy in a patient with PD shows volume loss in the midbrain with pale-staining substantia nigra and decreased size of the pars compacta. (Figure 3) Microscopically, there is depigmentation and loss of neurons. In some surviving neurons, there are cytoplasmic inclusion bodies with an eosinophilic core surrounded by a clear halo Lewy bodies. The Lewy body is not entirely specific but it is a highly sensitive marker for PD. (Figure 4). The presence of ï¡-synuclein in Lewy bodies in sporadic cases of PD suggests a central role for ï¡-synuclein in the pathogenesis of PD. Depletion of the dopaminergic neurons of the substantia nigra results in reduction of striatal dopamine, which is thought to be the main biochemical abnormality in PD. However, secondary pathological and biochemical alterations are considerably more widespread.The cause of PD is dopaminergic cell death. The discovery that a toxin 1-methyl-4-phenyl-1, 2, 3, 6 tetra- hydropyridine (MPTP) produces Parkinsonism in animals has stimulated a search for environmental agents that might be implicated in the pathogenesis of PD. PD is inherited in an autosomal dominant fashion in a small number of families, although most of these show atypical clinical features. Identification of a defective gene for ï¡-synuclein on chromosome 4q in a few families, combined with the fact that this protein is found in abundance in all Lewy bodies studied to date in sporadic cases, has opened a new avenue of research into the pathogenesis of PD. A second genetic locus on chromosome 2p is associated with more typical PD in a larger number of families. Rare pedigrees show an exclusively maternal inheritance pattern consistent with a defect in mitochondrial DNA.The course of PD is variable with subcortical dementia present in 30% and mood disorders in 50%. In some cases the course may be slow and in others rapidly progressive with severe disability occurring over a few years. The cornerstone of anti-Parkinsonian therapy is L-Dopa, the immediate natural precursor of dopamine, which is coverted to the deficient neurotransmitter by the enzyme aromatic amino acid decarboxylase. Surgical procedures for PD include pallidotomy, ventrolateral thalamotomy, and subthalamic or pallidal deep brain stimulation.1. Buttner-Ennever JA and Akert K. Medial rectus subgroups of the oculomotor nucleus and their abducens internuclear input in the monkey. J. Comp Neurol 1981;197:17-27. http://www.ncbi.nlm.nih.gov/pubmed/6894456 2. Buttner-Ennever JA, Horn AKE, Scherberger H and D'Ascanio P. Motoneurons of twitch and nontwitch extraocular muscle fibers in the abducens, trochlear and oculomotor nuclei of monkeys. J. Comp. Neurol. 2001;438:318-335. http://www.ncbi.nlm.nih.gov/pubmed/11550175 3. Leigh RJ, Zee DS. Diagnosis of Central Disorders of Ocular Motility, In The Neurology of Eye Movements, Fourth Edition. Oxford University Press, NY. 2006, Chp 8;343-372. 4. Mendez MF and Cummings JL. Dementia A Clinical Approach, Third Edition. Butterworth Heinemann 2003. 5. Wasicky R, Horn AKE and Buttner-Ennever JA. Twitch and nontwitch motoneuron subgroups of the medial rectus muscle in the oculomotor nucleus of monkeys receive different afferent projections. J. Comp. Neurol. 2004;479:117-129. http://www.ncbi.nlm.nih.gov/pubmed/15452829 6. White OB, Saint-Cyr JA, Sharpe, JA. Ocular Motor Deficits in Parkinson's Disease. 1. The Horizontal Vestibulo-Ocular Reflex and its Regulations. Brain 1983, 106;555-570. http://www.ncbi.nlm.nih.gov/pubmed/6640269 7. White OB, Saint-Cyr JA, Tomlinson D, Sharpe JA. Ocular Motor Deficits in Parkinson's Disease. II. Control of the Saccadic and Smooth Pursuit Systems. Brain 1983, 106;571-587. http://www.ncbi.nlm.nih.gov/pubmed/6640270 8 James Parkinson: http://www.whonamedit.com/doctor.cfm/392.htm