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Cerebellar Ataxia

Ataxia refers to a patient's inability to coordinate their movements and to maintain balance. Since those skills are mainly controlled by the cerebellum, lesions of this part of the central nervous system may result in cerebellar ataxia.


Presentation

As per definition, CA is a movement disorder associated with coordination and balance problems. These are most easily recognized while observing the patient's gait as well as their limb and eye movements. In detail, the following may be observed [7]:

  • Vertigo and dizziness
  • Imbalance and unsteady, staggering gait as well as impaired tandem gait
  • Hypotonia, tremor, dysdiadochokinesia, adysdiadochokinesia, grasping deficits and dysmetria, i.e., reduced muscle tones and involuntary contractions of muscles, the inability to rapidly perform alternating or targeted movements and to control motion ranges
  • Instability of ocular alignment, saccadic intrusions and nystagmus, smooth pursuit impairment
  • Abnormal vestibulo-ocular reflex

With regards to the patients life quality and if severe, these conditions may result in the inability to perform routine duties and may provoke frequent falls. In contrast, mild CA may only be noted while realizing determined tasks that require highly developed motor skills. Also, CA patients don't generally show all of the aforementioned symptoms.

The presence of additional symptoms may be helpful in identifying the cerebellum as the site of lesion: A patient presenting with ataxic dysarthria, for instance, is highly suspicious of cerebellar damage. Furthermore, cerebellar lesions often comprise cognitive and limbic regions and thus, corresponding non-motor neurological deficits may be observed, which in total have been referred to as Schmahmann's syndrome. They mainly consist in [8]:

  • Impaired planning and execution of everyday tasks, attention deficits
  • Disturbance of visual-spatial processing
  • Personality changes and behavioral disorders
  • Further issues regarding speech, writing and reading
Difficulty Walking
  • walking Speech disturbances with slurred speech and changes in tone, pitch, and volume Visual complaints Abnormal eye movements Headache Nausea and vomiting Lightheadedness Changes in mental state, such as personality or behavioral changes Chaotic eye[cookchildrens.org]
  • CASE A 51 year-old man presented to our hospital with nine-years history of progressive gait instability, difficulty walking and insulin dependent diabetes. Family history was unremarkable.[scielo.br]
  • The first indication generally is difficulty walking (gait ataxia). The condition typically progresses to the arms and trunk. Muscles weaken and waste away over time, causing deformities, particularly in your feet, lower legs and hands.[medtransacademy.com]
Episodic Weakness
  • We describe the molecular basis of a distinctive syndrome characterized by infantile stress-induced episodic weakness, ataxia, and sensorineural hearing loss, with permanent areflexia and optic nerve pallor.[ncbi.nlm.nih.gov]
Infectious Mononucleosis
  • ., acute cerebellar ataxia manifests few weeks after viral infection and infectious mononucleosis, influenza, measles or mumps) Intoxication with alcohol, illicit drugs or statins Neoplasm Nutritional deficiency (e.g., vitamins B12 and E, folate and copper[symptoma.com]
Progressive Dysphagia
  • He also had progressive dysphagia requiring gastrostomy tube for nutrition.[ncbi.nlm.nih.gov]
Macrocephaly
  • […] families who presented with recessively inherited moderate-severe intellectual disability, cerebellar ataxia, early-onset cerebellar atrophy, sensorineural hearing loss, and the distinctive association of progressively coarsening facial features, relative macrocephaly[ncbi.nlm.nih.gov]
Dysarthria
  • Spinocerebellar ataxias (SCAs) are a heterogeneous group of autosomal dominant cerebellar ataxias clinically characterized by progressive ataxia, dysarthria and a range of other concomitant neurological symptoms.[ncbi.nlm.nih.gov]
  • Cerebellar ataxia associated with glutamic acid decarboxylase autoantibodies (GAD-ab) is a rare and usually slow progressive disease with moderate to severe gait and limb ataxia, dysarthria, and nystagmus.[ncbi.nlm.nih.gov]
  • The results of examination were notable for severe dysarthria, slow saccades, a conspicuous dysmetria and dysdiadokokinesia. She had no cognitive, sensory or motor deficits. MRI revealed diffuse cerebellar atrophy.[ncbi.nlm.nih.gov]
  • A 12-year-old boy was admitted with severe ataxia, dysmetria, dysdiadokinesia, and dysarthria. He was diagnosed with acute post-infectious cerebellar ataxia (APCA).[ncbi.nlm.nih.gov]
  • A 45-year-old man with a cerebellar gait ataxia, dysmetria, nystagmus and mild cerebellar dysarthria was diagnosed with insulin-dependent diabetes mellitus a year after the onset of neurological symptoms.[ncbi.nlm.nih.gov]
Truncal Ataxia
  • ataxia, dysarthric speech and intention tremor), associated with cerebellar hypoplasia.[orpha.net]
  • The most common presenting sign was ataxic gait; however, truncal ataxia, action tremor, and dysmetria were also frequently seen.[medlink.com]
  • A broad range of signs and symptoms may be present: fever, tremor, nystagmus, truncal ataxia, dysarthria, headache, nausea, vomiting and consciousness alterations. Signs of meningeal irritation and seizures may be observed less frequently 1,4.[radiopaedia.org]
  • Truncal ataxia is predominant in cerebellar symptoms. The onset of cerebellar type of HE patients varied from acute to chronic.[dx.doi.org]

Workup

Diagnosis of CA and its underlying disease is based on thorough anamnesis, general and neurologic examination as well as neuroimaging. The former are particularly important since they may allow for a differentiation between spinal and cerebellar causes of ataxia, and because cerebellar lesions seen in images are often unspecific. For instance, it may not be possible to associate those findings to a determined entity without knowing if symptoms worsen progressively, or if the disease is characterized by episodes of remission and recurrence. Age is another key factor.

Virtually all patients with suspected CA should undergo magnetic resonance imaging (MRI) of the brain. Exceptions may be made for patients with a family history of a corresponding genetic disorder. With regards to MRI, the most common finding is cerebellar atrophy. Neuroimaging may also reveal the presence of a neoplasm or an abscess.

Depending on the results obtained so far, additional diagnostic measures may be necessary to determine the underlying disorder. If gene defects are suspected, samples for genetic screens have to be obtained.

Dyslipidemia
  • Mean age was 67.5 years old, predominantly male, with several comorbidities, such as dyslipidemia, diabetes mellitus, hypertension, and myocardial revascularization.[ncbi.nlm.nih.gov]

Treatment

Regeneration capacities of the central nervous systems are very limited. Accordingly, neurological deficits provoked by cerebellar lesions are often irreversible, and it is of great importance to initiate treatment as early as possible in order to avoid an aggravation of symptoms. Specific treatment options largely depend on the underlying disease and may range from dietary adjustments to drug therapy to surgical intervention. In any case, patients suffering from CA should participate in rehabilitation programs. Patients are to perform balance and coordination exercises to regain their ability to walk independently, to dominate their posture and to use their limbs in a controlled manner [9]. Frenkel exercises are often recommended to this end. Nevertheless, some patients may not be able to return to their everyday lives without using orthopedic aids [10].

With regards to symptomatic therapy of CA, modulators of serotonergic signaling may be applied. In particular, buspirone, an agonist of serotonin receptor 1A, is used to treat mild to moderate CA [11]. However, some patients may not respond to such treatment and this also applies to the use of serotonin reuptake inhibitors and antagonists of serotonin receptor 3 [12] [13]. Additionally, few studies suggest that administration of amantadine, memantine and riluzole may have beneficial effects [14].

More recent approaches to CA therapy involve transcranial direct current stimulation and magnetic stimulation of the cerebellum [15] [16]. Both aim at modulating the excitability of cerebellar neurons.

Prognosis

The life expectancy of CA patients is unaltered, unless cerebellar lesions are caused by diseases associated with a poor prognosis for life. Such may be the case in patients suffering from brain tumors. However, for many forms of CA, treatment options are very limited. Neuronal damage is frequently irreversible, but it may be possible to halt disease progression. Few diseases are associated with a very good prognosis. Acute cerebellar ataxia, for instance, is usually self-limiting and patients can expect to recover fully within few weeks [6].

Etiology

Congenital forms of CA are to be distinguished from acquired forms of the disease. With respect to the former, several genetic disorders have been related to cerebellar malfunction and consequent ataxia. Such diseases may be inherited with an autosomal recessive (ARCA), autsomal dominant (ADCA), X-linked or mitochondrial trait. Both ARCA and ADCA are heterogenous groups of neurodegenerative diseases, but the latter designations also comprise several entities. Some of those diseases pertaining to these four groups are listed below; the interested reader is referred to more extensive reviews available elsewhere [1] [2] [3].

To some extent, these diseases differ regarding their manifestation. For instance, loss of proprioception and pallesthesia as well as blunted reflexes are most commonly observed in ARCA.

Besides hereditary forms of CA, there are numerous other factors that may inflict cerebellar damage and thus provoke CA.

Of note, other classification systems than the one presented here exist. Forms of CA may also be assigned to distinct groups on the basis of the underlying pathophysiological mechanisms (e.g., metabolic and degenerative disorders), further involved anatomical structures (e.g., pure cerebellar and spinocerebellar diseases), the course of the disease (e.g., intermittent, persistent, chronic and progressive) as well as the mean age at symptom onset (early-onset vs. late-onset).

Epidemiology

Incidence and prevalence rates as well as gender, racial and age distribution patterns vary with different forms of CA. With regards to inherited CA, the most frequent disorder is Friedreich ataxia, which affects 1 in 30,000 to 50,000 people. CA due to multiple sclerosis, stroke, trauma or tumor are rather common forms of acquired CA. In sum, CA prevalence may amount to approximately 8 per 100,000 inhabitants, with 5 and 3 people suffering from hereditary and non-hereditary diseases, respectively [4].

While onset of symptoms related to genetic diseases typically occurs in infancy or childhood, the aforementioned forms of acquired CA is usually diagnosed in adults and the elderly. Children presenting with acquired ataxia most commonly suffer from acute cerebellar ataxia. It has been reported that the median age of CA symptom onset is in the fourth decade of life, but due to the aforementioned heterogeneity of disorders associated with CA, this statistical specification is of little relevance to clinical practice.

Sex distribution
Age distribution

Pathophysiology

Cerebellum and pons are the main parts of the metencephalon and this part of the brain is located in the posterior cranial fossa. The cerebellum plays a pivotal role in motor control and maintenance of balance and posture. From an anatomical point of view, it consists of three main portions, the anterior lobe, the posterior lobe and the flocculonodular lobe. These correspond only partially to the cerebellum's functional sections, which have been designated vestibulocerebellum, spinocerebellum and pontocerebellum: The vestibular system is connected to the vestibulocerebellum by sensory afferent nerves, and based on the input received, balance, posture and eye movements are coordinated. This function is complemented by the spinocerebellum, whose task is to process afferent stimuli originating from the spinal cord and muscle spindles, i.e., to control the position of limbs, trunk and head, and to adjust the muscle tone if necessary. Many complex movements require participation of the cerebral cortex and a connection between both structures is established by the pontocerebellum. Consequently, the single most characteristic symptom of cerebellar lesions is CA.

The molecular basis of CA varies widely. Since ion channels are of major importance for neuronal function, it is little surprising that several forms of CA are indeed channelopathies. Corresponding gene defects are often inherited with an autosomal dominant trait and affect calcium and potassium channels [5]. Such has been proven for ADCA episodic ataxia and spinocerebellar ataxia, but the pathomechanisms causing vestibulocerebellar syndrome are only poorly understood.

Prevention

For most forms of CA, no specific measures can be recommended. Since acute cerebellar ataxia is associated with viral infectious diseases, compliance with vaccination plans may reduce the individual risk of this disorder, though.

Summary

In general, the term ataxia describes a movement disorder characterized by a limited ability to maintain balance and posture, and/or to move limbs and eyes in a coordinated way. This description already implies that the clinical presentation of ataxic patients varies largely, and this may partially be explained by the fact that distinct parts of the central nervous system as well as subordinated structures are involved in planning and execution of a targeted movement. In detail, lesions of sensory pathways, spinal cord, basal ganglia, cerebellum and cerebral cortex may cause ataxia [1]. If cerebellar function is impaired and provokes such movement disorders, the patient is diagnosed with cerebellar ataxia (CA).

As is the case with lesions of any of the aforementioned structures, neurological deficits are rarely limited to ataxia in patients who sustained cerebellar damage. Besides CA, motor and coordination deficits of speech are observed frequently. Also, cognitive and affective functions may be impaired. Only the entirety of anamnestic data, neurological findings and data obtained by means of neuroimaging allow for associating an individual case with one of several differential diagnoses. As it is, CA may be related to genetic disorders, to inflammatory or immune-mediated pathophysiological processes, to neoplasms, trauma, vascular accidents or nutrient deficiencies.

Patient Information

In general, the term ataxia describes the patient's reduced ability to coordinate their movements, to maintain posture and balance. Complex neural circuits are involved in those processes and accordingly, ataxia may be triggered by a wide variety of lesions. In detail, functional impairment of sensory pathways, spinal cord, basal ganglia, cerebellum and cerebral cortex may cause ataxia. If ataxia occurs to pathophysiological events interfering with cerebellar function, the respective patient is diagnosed with cerebellar ataxia (CA).

CA may be provoked by genetic disorders, by autoimmune diseases, strokes, traumas and tumors, among others. CA typically manifests in form of vertigo and dizziness, an unsteady gait and problems upon controlling the movements of limbs and eyes. Moreover, cerebellar lesions are often associated with difficulties while speaking, writing and reading. All these symptoms are rather unspecific and in order to obtain more detailed information regarding the underlying disease, patients usually have to undergo magnetic resonance imaging and possibly additional procedures.

Only if a reliable diagnosis can be made, the appropriate therapeutic approach can be chosen. Causal treatment is available for few diseases associated with CA only, and symptomatic support may be provided in form of medication or surgery. Some patients, e.g., children suffering from post-infectious CA, have a very good prognosis, while others, namely those diagnosed with brain tumors, have a poor one.

References

Article

  1. Akbar U, Ashizawa T. Ataxia. Neurol Clin. 2015; 33(1):225-248.
  2. Tranchant C, Anheim M. Movement disorders in mitochondrial diseases. Rev Neurol (Paris). 2016.
  3. Fogel BL. Childhood cerebellar ataxia. J Child Neurol. 2012; 27(9):1138-1145.
  4. Joo BE, Lee CN, Park KW. Prevalence rate and functional status of cerebellar ataxia in Korea. Cerebellum. 2012; 11(3):733-738.
  5. Spillane J, Kullmann DM, Hanna MG. Genetic neurological channelopathies: molecular genetics and clinical phenotypes. J Neurol Neurosurg Psychiatry. 2016; 87(1):37-48.
  6. Nussinovitch M, Prais D, Volovitz B, Shapiro R, Amir J. Post-infectious acute cerebellar ataxia in children. Clin Pediatr (Phila). 2003; 42(7):581-584.
  7. Bodranghien F, Bastian A, Casali C, et al. Consensus Paper: Revisiting the Symptoms and Signs of Cerebellar Syndrome. Cerebellum. 2016; 15(3):369-391.
  8. Manto M, Marien P. Schmahmann's syndrome - identification of the third cornerstone of clinical ataxiology. Cerebellum Ataxias. 2015; 2:2.
  9. Kelly G, Shanley J. Rehabilitation of ataxic gait following cerebellar lesions: Applying theory to practice. Physiother Theory Pract. 2016:1-8.
  10. Abbud G, Janelle C, Vocos M. The use of a trained dog as a gait aid for clients with ataxia: a case report. Physiother Can. 2014; 66(1):33-35.
  11. Lou JS, Goldfarb L, McShane L, Gatev P, Hallett M. Use of buspirone for treatment of cerebellar ataxia. An open-label study. Arch Neurol. 1995; 52(10):982-988.
  12. Holroyd-Leduc JM, Liu BA, Maki BE, Zecevic A, Herrmann N, Black SE. The role of buspirone for the treatment of cerebellar ataxia in an older individual. Can J Clin Pharmacol. 2005; 12(3):e218-221.
  13. Ogawa M. Pharmacological treatments of cerebellar ataxia. Cerebellum. 2004; 3(2):107-111.
  14. Youn J, Shin H, Kim JS, Cho JW. Preliminary study of intravenous amantadine treatment for ataxia management in patients with probable multiple system atrophy with predominant cerebellar ataxia. J Mov Disord. 2012; 5(1):1-4.
  15. Benussi A, Koch G, Cotelli M, Padovani A, Borroni B. Cerebellar transcranial direct current stimulation in patients with ataxia: A double-blind, randomized, sham-controlled study. Mov Disord. 2015; 30(12):1701-1705.
  16. Koch G, D'Angelo E. Magnetic stimulation of the cerebellum. Moving towards the clinic. Funct Neurol. 2014; 29(1):5.

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Last updated: 2019-07-11 21:33