Oculomotor apraxia (OMA) is the absence or defect of controlled, voluntary, and purposeful

eye Eyes are organs of the visual system. They provide living organisms with vision, the ability to receive and process visual detail, as well as enabling several photo response functions that are independent of vision. Eyes detect light and conv ...

movement.Tada, M, Yokoseki, A, Sato, T, Makifuchi, T, Onodera, O. Early-onset ataxia with ocular motor apraxia and hypoalbuminemia/ataxia with oculomotor apraxia 1. Advances in Experimental Medicine and Biology 685 (2010): 21-33. It was first described in 1952 by the American ophthalmologist David Glendenning Cogan.Le Ber, I, Brice, A, Dürr, A. New autosomal recessive cerebellar ataxias with oculomotor apraxia. Current Neurology and Neuroscience Reports 5.5 (2005): 411-7. People with this condition have difficulty moving their eyes horizontally and moving them quickly. The main difficulty is in

saccade A saccade ( , French for ''jerk'') is a quick, simultaneous movement of both eyes between two or more phases of fixation in the same direction.Cassin, B. and Solomon, S. ''Dictionary of Eye Terminology''. Gainesville, Florida: Triad Publishi ...

initiation, but there is also impaired cancellation of the vestibulo-ocular reflex. Patients have to turn their head in order to compensate for the lack of eye movement initiation in order to follow an object or see objects in their

peripheral vision Peripheral vision, or ''indirect vision'', is vision as it occurs outside the point of fixation, i.e. away from the center of gaze or, when viewed at large angles, in (or out of) the "corner of one's eye". The vast majority of the area in the ...

, but they often exceed their target. There is controversy regarding whether OMA should be considered an

apraxia Apraxia is a motor disorder caused by damage to the brain (specifically the posterior parietal cortex or corpus callosum), which causes difficulty with motor planning to perform tasks or movements. The nature of the damage determines the disorder' ...

, since apraxia is the inability to perform a learned or skilled motor action to command, and saccade initiation is neither a learned nor a skilled action.Galvaez-Jimenez N, Tuite P, Bhatia K, editors. Uncommon Causes of Movement Disorders. New York: Cambridge University Press; 2011:38-40.

Symptoms

* Absence of fast phase

nystagmus Nystagmus is a condition of involuntary (or voluntary, in some cases) eye movement. Infants can be born with it but more commonly acquire it in infancy or later in life. In many cases it may result in reduced or limited vision. Due to the invol ...

on horizontal optokinetic testing * Problems in nerve function involved in eye movement control, called

neuropathy Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or o ...

* Inability to visually follow objects * Head thrusts to compensate for the inability to accomplish voluntary horizontal gaze .

Causes

OMA is a neurological condition. Although some brain imaging studies of people with OMA reveal a normal brain, some MRI studies have revealed unusual appearance of some brain areas, in particular the corpus callosum, cerebellum, and/or fourth ventricle. Oculomotor apraxia can be acquired or

congenital A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can ...

. Sometimes no cause is found, in which case it is described as

idiopathic An idiopathic disease is any disease with an unknown cause or mechanism of apparent wikt:spontaneous, spontaneous origin. From Ancient Greek, Greek ἴδιος ''idios'' "one's own" and πάθος ''pathos'' "suffering", ''idiopathy'' means approxi ...

A person may be born with the parts of the brain for eye movement control not working, or may manifest poor eye movement control in childhood. If any part of the brain that controls eye movement becomes damaged, then OMA may develop. One of the potential causes is bifrontal hemorrhages. In this case, OMA is associated with bilateral lesions of the

frontal eye fields The frontal eye fields (FEF) are a region located in the frontal cortex, more specifically in Brodmann area 8 or BA8, of the primate brain. In humans, it can be more accurately said to lie in a region around the intersection of the middle fronta ...

(FEF), located in the caudal middle frontal gyrus. The FEF control voluntary eye movements, including saccades, smooth pursuit and vergence. OMA can also be associated with bilateral hemorrhages in the parietal eye fields (PEF). The PEF surround the posterior, medial segment of the intraparietal sulcus. They have a role in reflexive saccades, and send information to the FEF. Since the FEF and PEF have complementary roles in voluntary and reflexive production of saccades, respectively, and they get inputs from different areas of the brain, only bilateral lesions to both the FEF and PEF will cause persistent OMA. Patients with either bilateral FEF or bilateral PEF damage (but not both FEF and PEF) have been shown to regain at least some voluntary saccadic initiation some time after their hemorrhages. Other causes of OMA include brain tumors and cardiovascular problems,.

Ataxia with oculomotor apraxia

A subgroup of genetically recessive

ataxia Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of ...

s associated with OMA has been identified, with an onset during childhood. These are ataxia with oculomotor apraxia type 1 (AOA1), ataxia with oculomotor apraxia 2 (AOA2), and

ataxia telangiectasia Ataxia is a neurological sign consisting of lack of voluntary Motor coordination, coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicati ...

. These are autosomal recessive disorders and the associated gene products are involved in DNA repair. Both horizontal and vertical eye movements are affected in these disorders. Although people with either type may have some mild cognitive problems, such as difficulty with concentration or performing multi-step activities, intellectual function is usually not affected.Criscuolo, C, Chessa, L, Di Giandomenico, S, Mancini, P, Saccà F,, Grieco, G, Piane, M, Barbieri, F, De Michele, G, Banfi, S, Pierelli, F, Rizzuto, N, Santorelli, F, Gallosti, L, Filla, A, Casali, C. Ataxia with oculomotor apraxia type 2: a clinical, pathologic, and genetic study. Neurology 66.8 (2006)):1207-10.

Type 1

Ataxia-oculomotor apraxia type 1 (AOA1) usually has an onset of symptoms during childhood. It is an autosomal recessive cerebellar ataxia (ARCA) associated with hypoalbuminemia and hypercholesterolemia. Mutations in the gene

APTX aptX (''apt'' stands for ''audio processing technology'') is a family of proprietary audio codec An audio codec is a device or computer program capable of encoding or decoding a digital data stream (a codec) that encodes or decodes audio. In s ...

, which encodes for

aprataxin Aprataxin is a protein that in humans is encoded by the ''APTX'' gene. This gene encodes a member of the histidine triad (HIT) superfamily, some of which have nucleotide-binding and diadenosine polyphosphate hydrolase activities. The encoded pro ...

, have been identified to be responsible for AOA1. Elevated

creatine kinase Creatine kinase (CK), also known as creatine phosphokinase (CPK) or phosphocreatine kinase, is an enzyme () expressed by various tissues and cell types. CK catalyses the conversion of creatine and uses adenosine triphosphate (ATP) to create phosp ...

is occasionally present, in addition to a sensorimotor axonal neuropathy, as shown by nerve conduction velocity studies. In addition, MRI studies have shown cerebellar atrophy, mild brainstem atrophy, and, in advanced cases, cortical atrophy The

protein APTX can remove obstructive termini from DNA strand breaks that interfere with

DNA repair DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA dam ...

. APTX is recruited to DNA single-strand breaks by

XRCC1 DNA repair protein XRCC1, also known as X-ray repair cross-complementing protein 1, is a protein that in humans is encoded by the ''XRCC1'' gene. XRCC1 is involved in DNA repair, where it complexes with DNA ligase III. Function XRCC1 is invol ...

protein, where it functions as a nick sensor to scan the single-strand breaks for 5’-AMP obstructive termini that are intermediates in failed

DNA ligase DNA ligase is a specific type of enzyme, a ligase, () that facilitates the joining of DNA strands together by catalyzing the formation of a phosphodiester bond. It plays a role in repairing single-strand breaks in duplex DNA in living organ ...

reactions. The removal of these obstructions allows DNA repair of the break to be completed. It is not yet clear which specific single-strand breaks are the

neurodegenerative A neurodegenerative disease is caused by the progressive loss of structure or function of neurons, in the process known as neurodegeneration. Such neuronal damage may ultimately involve cell death. Neurodegenerative diseases include amyotrophic ...

agents in AOA1 patients that lack functional

protein. However single-strand breaks with 5’-AMP termini appear to be the most likely candidate lesion.

Type 2

Ataxia-oculomotor apraxia type 2 (AOA2), also known as spinocerebellar ataxia with axonal neuropathy type 2, has its onset during adolescence. It is characterized by cerebellar atrophy and peripheral neuropathy. Sufferers of Type 2 have high amounts of another protein called

alpha-fetoprotein Alpha-fetoprotein (AFP, α-fetoprotein; also sometimes called alpha-1-fetoprotein, alpha-fetoglobulin, or alpha fetal protein) is a protein that in humans is encoded by the ''AFP'' gene. The ''AFP'' gene is located on the ''q'' arm of chromosome 4 ...

(AFP), and may also have high amounts of the protein

creatine phosphokinase Creatine kinase (CK), also known as creatine phosphokinase (CPK) or phosphocreatine kinase, is an enzyme () expressed by various tissues and cell types. CK catalyses the conversion of creatine and uses adenosine triphosphate (ATP) to create phosp ...

(CPK). Mutations in the

SETX Probable helicase senataxin is an enzyme that in humans is encoded by the ''SETX'' gene. This gene encodes a protein named senataxin, a 302kDa protein Sequence and structure There is high homology between human SETX and yeast Sen1. Sen1 in ye ...

gene are the cause of the disease. AOA2 shows cerebellar atrophy, loss of

Purkinje cells Purkinje cells, or Purkinje neurons, are a class of GABAergic inhibitory neurons located in the cerebellum. They are named after their discoverer, Czech anatomist Jan Evangelista Purkyně, who characterized the cells in 1839. Structure The ...

, and demyelination. In particular, there is a failure of the cerebrocerebellar circuit in AOA2 that has been shown to be responsible for the weaker coordination of complex cognitive functions such as working memory, executive functions, speech, and sequence learning. Although there is no sign of mental retardation or severe dementia, even after long disease duration, research on families with possible AOA2 have shown mild cognitive impairment as indexed by the Mini-Mental State Examination (MMSE) and the Mattis Dementia Rating Scale. These impairments appear to be mostly due to a deficit in initiation and concept subtests,.Klivényi, P, Nemeth, D, Sefcsik, T, Janacsek, K, Hoffmann, I, Haden, G, Londe, Z, Vecsei, L. Cognitive functions in ataxia with oculomotor apraxia type 2. Frontiers in Neuro-ophthalmology 3 (2012):125.

Ataxia telangiectasia

Telangiectasia Telangiectasias, also known as spider veins, are small dilated blood vessels that can occur near the surface of the skin or mucous membranes, measuring between 0.5 and 1 millimeter in diameter. These dilated blood vessels can develop anywhere on ...

s are widened blood vessels that can develop anywhere on the skin, mucous membranes, whites of the eyes, and even in the brain. Telangiectasias are associated with multiple systemic signs, the most serious of which are unusual sensitivity to ionizing radiation, excessive chromosomal breakage, and a deficiency in the immune system.

Ataxia telangiectasia Ataxia is a neurological sign consisting of lack of voluntary Motor coordination, coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicati ...

results from defects in the

ataxia telangiectasia mutated ATM serine/threonine kinase or Ataxia-telangiectasia mutated, symbol ATM, is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks. It phosphorylates several key proteins that initiate activation of the DNA ...

gene, which can cause abnormal cell death in various places of the body, including brain areas related to coordinated movement of the eyes. Patients with ataxia telangiectasia have prolonged vertical and horizontal saccade latencies and hypometric saccades, and, although not all, some patients show head thrusts,.Saunders-Pullman, R, Raymond, D, Stoessl,, A, Hobson, D, Nakamura, T, Pullman, S, Lefton, D, Okun, M, Uitti, R, Sachdev, R, Stanley, K, San Luciano, M, Hagenah, J, Gatti, R, Ozelius, L, Bressman, S. Variant ataxia-telangiectasia presenting as primary-appearing dystonia in Canadian Mennonites. Neurology 78.13 (2012):1029.

Diagnosis

References

{{Reflist Eye diseases