Cerebellar Ataxia

Introduction

Cerebellar Ataxia (CA) is the lack of coordination and regulation of muscle movement. The cerebellum is responsible for the maintenance of balance and posture, coordination of voluntary movements, and some cognitive functions. Strokes, disease, or tumors located on or near the cerebellum will result in symptoms such as slurred words, fumbling with fine motor control, a drunken gait, and a lack of coordination in movement. Lesion is a broad term which refers to any pathological or traumatic discontinuity of tissue or loss of function of a part. [1] Traumatic disease or tumor are not the only cause of CA, there have been studies and reports of patients who have inherited Cerebellar Ataxia.[8]. There are three different genetic types (I, II, & III) referred to as Autosomal Dominant Cerebellar Ataxia (ADCA) [7]. Regardless of etiology there is a lesion in the cerebellum that has caused an inability of the cerebellum to perform its normal function which leads to an ataxia. CA is a devastating disorder that can lead to life-long challenge in performing everyday movements and can result in emotional distress. Without a properly functioning cerebellum the individual will still be able to perform movement, but will lose the ability to coordinate movements. In this video we can see a patient who is struggling with an Ataxic Gait and it is clear how difficult everyday situations become for patients with cerebellar ataxia

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Image 1

















Functional Anatomy

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Image 3

The cerebellum is located at the back of the brain, seated on the foramen magnum, directly
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Image 2

underneath the dura-matter, and just dorsal to the pons as we see in image 2 below. The cerebellum is divided into three lobes (image 1) by the posterolateral and primary fissures. The primary fissure divides the anterior lobe from the posterior lobe while the posterior fissure divides the posterior lobe from the flocculonodular lobe. Image 1 presents the cerebellum as flattened for visualization purposes, but in actuality the flocculonodular lobe is pushed directly up against the brain stem as the cerebellum has a curled appearance (image3). There are two major parts of the cerebellum, the cerebellar cortex and the cerebellar deep nuclei. The cerebellar cortex is responsible for processing all information coming into the cerebellum and then relaying this processed information to the deep cerebellar nuclei. The deep cerebellar nuclei are responsible for most of the output from the cerebellum. Thus, a lesion to the cerebellar nuclei has the same effect as a complete lesion of the entire cerebellum [2].

-Cerebellar Cortex
The cerebellar cortex is a large surrounding tissue sheet covering the white matter of the cerebellum with the gray matter being the external sheet. The gray matter is divided into three layers as well; the most external layer is the molecular layer, the middle layer is the purkinje cell layer, and the deepest layer that is in contact with the white matter is the granular layer. [10] Each of these layers is comprised with specific cells to that layer with the ultimate goal of projecting out through the purkinje cell into the deep cerebellar nuclei. Two crucial differences noted between the cerebellar cortex and the cerebral cortex does not contribute directly to consciousness and the hemispheres posses ipsilateral representation of the body parts [11]. The cerebellar cortex has a narrow medial zone called the vermis that lies between the intermediate hemisphere and the lateral hemispheres. Each of these three zones also contain the three layers of the cerebral cortex. The vermis, also referred to as the medial zone, is involved in movement of the proximal regions of the body such as the neck, shoulder, and trunk. According to a study done to challenge previous thinking on the input into the cerebellum, it was concluded that input from the dorsal spinocerebellar tract to the vermis originates from regions of arm, leg, and proximal body representation in multiple cortical areas. [9] The intermediate hemisphere, or intermediate zone (paravermis), has influence over the distal parts of the limbs, especially the hands and the feet. Finally the lateral hemispheres are involved in the planning of sequential movements of the entire body and involved with the conscious assessment of movement errors. [11]

-Cerebellar Deep Nuclei
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Image 4

Deep to the cerebellar cortex within the white matter are four masses of gray matter on each side of the mid-line. These are referred to as the deep cerebellar nuclei and are responsible for the output of the cerebellum. The input comes in from the purkinje cells and then travels out on afferent fibers to a few different places. The most medial nuclei is the fastigial and it is located near the mid-line in the vermis region of the cerebellum. The majority of its input will be received from the vermis. The emboliform and the globose nuclei are two separate nucleus but together they are referred to as the interposed nuclei. The input to the interposed nuclei is coming from the paravermal region, traveling through purkinje fibers. The largest and most lateral of the deep cerebellar nuclei is the dentate nucleus. It has a long wrinkling appearance and is receiving input from the lateral hemispheres of the cerebellar cortex [10]. Each of these nuclei receive excitatory impulses from the mossy and climbing fibers and inhibitory impulses from the purkinje cells.


Neuronal Connections

The purkinje cells are responsible from transmitting impulses from the cerebral cortex to the main output nuclei, which are the deep cerebellar nuclei. Each of these have efferent axons exiting the cerebellum and going to either the red nucleus, thalamus, vestibular nuclei, and/or the reticular formation.
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Image 6


-Fastigial Nucleus
The most medial nuclei is the fastigial nucleus which receives its input from the vermis. The vermis receives its input from the vestibular system, the proximal somatosensory, the auditory, and the visual system. Any information that is processed in the vermis is then relayed to the fastigial nucleus. The fastigial nucleus then has output to the reticular formation and to the vestibular nuclei which travels out of the cerebellum through the inferior peduncle (Image 6) . [2] Output traveling to the vestibular nuclei reach both the ipsilateral and contralateral sides. From the vestibular nuclei the impulse travels down the vestibulospinal tract to ipsilateral motor neurons eventually influencing extensor muscle tone. The axons that synapse at the reticular formation are ultimately influencing ipsilateral motor activity in spinal segments through the reticulospinal tract. [10]
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Image 5





-The Interposed Nuclei
The interposed nuclei contain both the globos and emboliform nuclei. The intermediate hemispheres receive and process information mainly from the spinal tracts, proximal somatosensory, auditory information, and visual information. [2] Output from the globos and emboliform nuclei travel through the superior peduncle and decussate to the contralateral red nucleus. The red nucleus is the origin of the rubrospinal tract which decussates, so the interposed nucleus influence ipsilateral motor activity.

-The Dentate Nucleus
The dentate nucleus receives input from the lateral hemispheres. The information coming into the lateral hemispheres are corticopontine cerebellar inputs, which is information regarding the motor planning of a requested movement. Corticopontine means that the information is coming from the cortical area of the brain, mostly premotor or motor, and goes through the pontine nucleus before entering into the cerebellum through the middle cerebellar peduncle. Image 5 highlights the corticopontine fiber in green showing the pathway it follows into the cerebellum. Once the lateral hemisphere processes this information it is then relayed to the dentate nucleus. The efferent axons travel out of the cerebellum through the superior peduncle and synapse in the contralateral ventrolateral nucleus of the thalamus [10]. Thalamic nuclei then project into the motor cortex where the dentate can influence the motor activity. Descending tracts will decussate indicating that the dentate nucleus is also influencing ipsilateral motor activity.

-The flocculonodular lobe
The flocculonodular lobe does not have deep nuclei but it has surrogate deep nuclei, which are the vestibular nuclei. The afferent pathways coming from the vestibular nuclei travel through the inferior peduncle and to the flocculonodular lobe, where they are processed. The floccular region is receiving input conveying signal related to retinal image slip, head movement, and eye movements. [4] After the information is processed the output travels back to the vestibular nuclei to help produce smooth ocular following eye movements and modifying the vestibular ocular reflex during visual-vestibular conflict. [5] The vestibular nuclei that is innervated by the flocculonodular lobe has vestibulospinal projects and vestibule-ocular projection that descend and ascend in the medial longitudinal fasciculus (MLF). The axons in the MLF innervate the motor neurons that control the axial muscles and the external ocular muscles. [10]

Cerebellar Ataxia

Patients with cerebellar dysfunction have an incoordination or clumsiness of movement. This lack of coordination is called ataxia. Patients dealing with
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Table 1
cerebellar ataxia have difficulty regulating force, range, direction, velocity, and rhythm of muscle contractions [6]. Lesions in the three different lobes will show ataxic symptoms in different manors or areas of the body. For example anterior and flocculonodular lobe will lead to oculomotor and balance impairments, with gait ataxia. If a lesion is in or near the vermis there will be gait and trunk ataxia since most of the output is directed at the primary somatosensory areas. [6] In the book Clinical Neuroscience the authors mention three different ataxic syndromes; anterior lobe syndrome, flocculonodular lobe syndrome, and posterior lobe syndrome. Cerebellar ataxia is the broad term that could refer to any number of diseases or disorders that originate from the cerebellum.

-Lesions in the Anterior Lobe
The anterior lobe has functional responsibility associated with the vermis and paravermal regions. Each of these regions as discussed previously directly influence the ipsilateral motor activity of the proximal spinal motor neurons. Therefore the anterior lobe is responsible for coordinating and regulating trunk and
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Image 7
limb movement as it occurs [11]. Degeneration or lesions located in the anterior lobe would lead to ataxia of the gait which cause the patient to be perceived in a drunken state. There is clumsiness and uncoordinated movements of the lower limbs as they attempt to walk, which is demonstrated in image 7. In the videopresented earlier we saw an example of a patient demonstrating an ataxic gait cycle. The motor cortex would still continue to send motor commands the the neurons of the trunk, but the coordination and regulation would be blocked due to the lesion in the anterior lobe resulting in an ataxic gait.

-Lesions in the Flocculonodular Lobe
The flocculonodular lobe has projections to the vestibular nuclei that ultimately innervate the motor neurons of the axial muscles and the external ocular muscles. Lesions in this lobe will result in a lack
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Image 8
of control over axial muscles that causes the patient to walk on a wide base with the trunk reeling from side to side as seen in image 8. This drift from side to side is called lateropropulsion and will tend to drift towards the side of the lesion[3,10]. In the video below we see an example of a wide based gait with the reeling from side to side as the patient struggles to coordinate the axial trunk.


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Image 9

-Lesions in the Posterior Lobe
Lesions or tumors in the posterior lobe will result in a loss of coordination in voluntary movements. Dysdiadochokinesia is the inability to perform rapid alternating movements such as repetitive pronation and supination [11]. This difficulty will occur on the side of the body that the lesion is on due to the ipsilateral influence of the posterior lobe in the cerebellum. In this video showing dysdiadochokinesia there is a clear example of a patient struggling with the repeated supination and pronation of the hand. In posterior lobe lesions we also see patients struggling with unsteadiness of the hand as the reach for an intended object as demonstrated in image 9. When the patient reaches for the glass obtain an unsteady tremor that is perpendicular to direction of movement. A common test for this is having the patient reach to touch their nose. If they have cerebellar ataxia they will develop this perpendicular tremor and not be able to smoothly located the tip of the nose.



















Summary

Ataxia is most commonly recognized in the gait cycle but can be seen in posture, voluntary movements, and anything that is under the control of the cerebellum. Unstable body segments characterize ataxia of stance, as the trunk tends to lurch from side to side. Gait ataxia is defined as irregular and broad-based, with unequal steps and multiple corrections. The lesion can be located in any of the lobes or regions in the cerebellum and each lesion will lead to a different ataxic example. The cerebellum is crucial in coordinating and regulating smooth motor function, but it is not required to produce movement. A patient will be able to produce movement with a total lack of the cerebellum. Much has been learned about the cerebellum and continued research will unveil more about its function and its production of coordinated movements.

Glossary

Ataxia - lack of voluntary coordination of muscle movements
Lesion - any pathological or traumatic discontinuity of tissue or loss of function of a part
Purkinje Cell - large neuron with many branching extensions that is found in the cortex of the cerebellum of the brain and that plays a fundamental role in controlling motor movement.
Dorsal Spinal Cerebellar Tract - conveys proprioceptive information from proprioceptors in the skeletal muscles and joints to the cerebellum.
White Matter - is a component of the central nervous system, in the brain and superficial spinal cord, and consists mostly of glial cells and myelinated axons

that transmit signals from one region of the cerebrum to another and between the cerebrum and lower brain centers.
Dysdiadochokinesia - an impaired ability to perform rapid, alternating movements

Quiz

-True and False
1. Purkinje cells are the main projection cells from the cerebellar cortex to the deep cerebellar nuclei (T/F)
2. The three lobes of the cerebellum are the Anterior lobe, Inferior lobe, and flocculonodular lobe (T/F)
3. The fastigial nuclei have input to the reticular formation and the vestibular nuclei (T/F)
4. The deep cerebellar nuclei is responsible for the output of the cerebellum (T/F)
5. The cerebellum is solely responsible for locomotion. (T/F)

-Short Answer
1. Which nucleus is located most laterally in the cerebellum?
2. Dysdiadochokinesia is a disorder mainly associated with which lobe?
3. The afferent and efferent fibers of the cerebellum travel through three landmarks called ?
4. The most medial region of the cerebellum is called what? For its similar appearance to a what?
5. The lack of voluntary coordination of muscle movements is called what?



Suggested Readings

-Steve G. Massaquoi, MD, PhD, Harvard Medical School, Department of Neurology, Massachusetts General Hospital, CPZS-340, 55 Fruit Street, Boston, MA 02114, USA. Tel: 617-726-3216 (not used in introduction
Quiz

-Young PA, Young HA, Tolbert DL. The Cerebellum: Ataxia. p.103-120 Clinical Neuroscience 2nd edition, 2008.

-Snell, S. Richard. Clinical Neuronanatomy 6th edition. The Cerebellum and its Connections. P219-241

-Gilman S, Bloedal J, Lechtenberg R. The symptoms and signs of cerebellar disease. In: Disorders of the Cerebellum. Philadelphia, Pa: FA Davis Co; 1981: Contemporary Neurology series.

References
[2]. Cerebellum (Section 3, Chapter 5) Neuroscience Online: An Electronic Textbook for the Neurosciences | Department of Neurobiology and Anatomy - The University of Texas Medical School at Houston. Retrieved December 1, 2015. http://neuroscience.uth.tmc.edu/s2/chapter04.html


[9]. Coffman, Keith, Richard Dum, and Peter Strick. "Cerebellar Vermis Is a Target of Projections from the Motor Areas in the Cerebral Cortex." Cerebellar Vermis Is a Target of Projections from the Motor Areas in the Cerebral Cortex. Ed. Ann Graybiel. Web. 1 Dec. 2015.

[8]. Di Bella, Daniela, et al. "Mutations in the mitochondrial protease gene AFG3L2 cause dominant hereditary ataxia SCA28." Nature Genetics 42.4 (2010): 313+. Academic OneFile. Web. 30 Nov. 2015.

[6]. Gill-Body, Kathleen, Rita Popat, and Stephen Parker. "Rehabilitation of Balance in Two Patients With Cerebellar Dysfunction." Journal of the American Physical Therapy Association. Accessed November 30, 2015. http://ptjournal.apta.org/content/77/5/534.full.pdf.

[3]. Gilman S, Bloedal J, Lechtenberg R. The symptoms and signs of cerebellar disease. In: Disorders of the Cerebellum. Philadelphia, Pa: FA Davis Co; 1981: Contemporary Neurology series.

[1]."Lesion." TheFreeDictionary.com. Web. 30 Nov. 2015.

[10]. Snell, S. Richard. Clinical Neuronanatomy 6th edition. The Cerebellum and its Connections. P219-241

[4]. T Belton, R A McCrea. 2000 Role of the cerebellar flocculus region in cancellation of the VOR during passive whole body rotation (0)

[5]. Takemori S and Cohen B. loss of visual suppression of vestibular nystagmus after flocculus lesion. Brain res 72: 213-234, 1974

[7]. Whaley, Nathaniel Robb, Shinsuke Fujioka, and Zbigniew K. Wszolek. "Autosomal dominant cerebellar ataxia type I: A review of the phenotypic and genotypic characteristics." Orphanet Journal of Rare Diseases 6 (2011): 33. Academic OneFile. Web. 30 Nov. 2015.

[11]. Young PA, Young HA, Tolbert DL. The Cerebellum: Ataxia. p.103-120 Clinical Neuroscience 2nd edition, 2008.

Images References

Image. 1 http://tse3.mm.bing.net/th?id=OIP.M6d3f50e9b78b9f59407906285d587f93H0&pid=15.1

Image 2. http://www.heartandstroke.com/atf/cf/%7B99452D8B-E7F1-4BD6-A57D-B136CE6C95BF%7D/anatomy_ofthe_brain.jpg

Image 3. Young PA, Young HA, Tolbert DL. The Cerebellum: Ataxia. p.104 Clinical Neuroscience 2nd edition, 2008.

Image 4. Snell, S. Richard. Clinical Neuronanatomy 6th edition. The Cerebellum and its Connections. P224, 2006.

Image 5. http://www.eneurosurgery.com/wpimages/wpa737a936.png

Image 6. http://what-when-how.com/wp-content/uploads/2012/04/tmp15F121.jpg

Image 7. Young PA, Young HA, Tolbert DL. The Cerebellum: Ataxia. p.117 Clinical Neuroscience 2nd edition, 2008.

Image 8. Young PA, Young HA, Tolbert DL. The Cerebellum: Ataxia. p.119 Clinical Neuroscience 2nd edition, 2008.

Image 9. Young PA, Young HA, Tolbert DL. The Cerebellum: Ataxia. p.112 Clinical Neuroscience 2nd edition, 2008.

Answers to Quiz Questions

1. T
2. F
3. T
4. T
5. F
6. Dentate
7. Posterior
8. Peduncles
9. Vermis, worm
10. Ataxia