Ataxia

Ataxia
A form of ataxia commonly occurs in Parkinson's disease
SpecialtyNeurology
SymptomsTrouble walking, trouble talking, abnormal eye movements[1]
ComplicationsChoking, pressure ulcers, depression.[1]
TypesCerebellar, sensory, vestibular[1]
CausesAlcohol, brain tumors, stroke, multiple sclerosis, hypothyroidism, head injury, certain medications, certain genetic conditions[1]
TreatmentDepends on the underlying cause[1]

Ataxia is a neurological sign consisting of lack of coordination of muscle movement.[1] This can result in trouble walking, trouble talking, and abnormal eye movements.[1] Complications may include choking, pressure ulcers, or depression.[1]

It may occur due to alcohol, brain tumors, stroke, multiple sclerosis, hypothyroidism, head injury, certain medications, and certain genetic conditions.[1] Genetic conditions include Friedreich ataxia and Wilson disease.[1] The underlying mechanism involves problems with the parts of the nervous system that coordinate movement.[1] It can be divided into three types cerebellar, sensory, and vestibular.[1]

Treatment depends on the underlying cause.[1] There is no cure for inherited cases.[1] Efforts to manage the condition may include walking aids and physical therapy.[1] Ataxia affects about 26 per 100,000 children.[1] The word is from Greek α- [a negative prefix] + -τάξις [order] = "lack of order".[2]

Types

Cerebellar

See also: Cerebellar ataxia

The term cerebellar ataxia is used to indicate ataxia due to dysfunction of the cerebellum.[3] The cerebellum is responsible for integrating a significant amount of neural information that is used to coordinate smoothly ongoing movements and to participate in motor planning. Although ataxia is not present with all cerebellar lesions, many conditions affecting the cerebellum do produce ataxia.[4] People with cerebellar ataxia may have trouble regulating the force, range, direction, velocity, and rhythm of muscle contractions.[5] This results in a characteristic type of irregular, uncoordinated movement that can manifest itself in many possible ways, such as asthenia, asynergy, delayed reaction time, and dyschronometria.[6] Individuals with cerebellar ataxia could also display instability of gait, difficulty with eye movements, dysarthria, dysphagia, hypotonia, dysmetria, and dysdiadochokinesia.[4] These deficits can vary depending on which cerebellar structures have been damaged, and whether the lesion is bi- or unilateral.

People with cerebellar ataxia may initially present with poor balance, which could be demonstrated as an inability to stand on one leg or perform tandem gait. As the condition progresses, walking is characterized by a widened base and high stepping, as well as staggering and lurching from side to side.[4] Turning is also problematic and could result in falls. As cerebellar ataxia becomes severe, great assistance and effort are needed to stand and walk.[4] Dysarthria, an impairment with articulation, may also be present and is characterized by "scanning" speech that consists of slower rate, irregular rhythm, and variable volume.[4] Also, slurring of speech, tremor of the voice, and ataxic respiration may occur. Cerebellar ataxia could result with incoordination of movement, particularly in the extremities. Overshooting (or hypermetria) occurs with finger-to-nose testing and heel to shin testing; thus, dysmetria is evident.[4][7] Impairments with alternating movements (dysdiadochokinesia), as well as dysrhythmia, may also be displayed. Tremor of the head and trunk (titubation) may be seen in individuals with cerebellar ataxia.[4]

Dysmetria is thought to be caused by a deficit in the control of interaction torques in multijoint motion.[8] Interaction torques are created at an associated joint when the primary joint is moved. For example, if a movement required reaching to touch a target in front of the body, flexion at the shoulder would create a torque at the elbow, while extension of the elbow would create a torque at the wrist. These torques increase as the speed of movement increases and must be compensated and adjusted for to create coordinated movement. This may, therefore, explain decreased coordination at higher movement velocities and accelerations.

  • Dysfunction of the vestibulocerebellum (flocculonodular lobe) impairs balance and the control of eye movements. This presents itself with postural instability, in which the person tends to separate his/her feet upon standing, to gain a wider base and to avoid titubation (bodily oscillations tending to be forward-backward ones). The instability is, therefore, worsened when standing with the feet together, regardless of whether the eyes are open or closed. This is a negative Romberg's test, or more accurately, it denotes the individual's inability to carry out the test, because the individual feels unstable even with open eyes.
  • Dysfunction of the spinocerebellum (vermis and associated areas near the midline) presents itself with a wide-based "drunken sailor" gait (called truncal ataxia),[9] characterised by uncertain starts and stops, lateral deviations, and unequal steps. As a result of this gait impairment, falling is a concern in patients with ataxia. Studies examining falls in this population show that 74–93% of patients have fallen at least once in the past year and up to 60% admit to fear of falling.[10][11]
  • 'Dysfunction of the cerebrocerebellum' (lateral hemispheres) presents as disturbances in carrying out voluntary, planned movements by the extremities (called appendicular ataxia).[9] These include:
    • Intention tremor (coarse trembling, accentuated over the execution of voluntary movements, possibly involving the head and eyes, as well as the limbs and torso)
    • Peculiar writing abnormalities (large, unequal letters, irregular underlining)
    • A peculiar pattern of dysarthria (slurred speech, sometimes characterised by explosive variations in voice intensity despite a regular rhythm)
    • Inability to perform rapidly alternating movements, known as dysdiadochokinesia, occurs, and could involve rapidly switching from pronation to supination of the forearm. Movements become more irregular with increases of speed.[12]
    • Inability to judge distances or ranges of movement happens. This dysmetria is often seen as undershooting, hypometria, or overshooting, hypermetria, the required distance or range to reach a target. This is sometimes seen when a patient is asked to reach out and touch someone's finger or touch his or her own nose.[12]
    • The rebound phenomenon, also known as the loss of the check reflex, is also sometimes seen in patients with cerebellar ataxia, for example, when patients are flexing their elbows isometrically against a resistance. When the resistance is suddenly removed without warning, the patients' arms may swing up and even strike themselves. With an intact check reflex, the patients check and activate the opposing triceps to slow and stop the movement.[12]
    • Patients may exhibit a constellation of subtle to overt cognitive symptoms, which are gathered under the terminology of Schmahmann's syndrome.[13]

Sensory

The term sensory ataxia is used to indicate ataxia due to loss of proprioception, the loss of sensitivity to the positions of joint and body parts. This is generally caused by dysfunction of the dorsal columns of the spinal cord, because they carry proprioceptive information up to the brain. In some cases, the cause of sensory ataxia may instead be dysfunction of the various parts of the brain that receive positional information, including the cerebellum, thalamus, and parietal lobes.

Sensory ataxia presents itself with an unsteady "stomping" gait with heavy heel strikes, as well as a postural instability that is usually worsened when the lack of proprioceptive input cannot be compensated for by visual input, such as in poorly lit environments.

Physicians can find evidence of sensory ataxia during physical examination by having patients stand with their feet together and eyes shut. In affected patients, this will cause the instability to worsen markedly, producing wide oscillations and possibly a fall; this is called a positive Romberg's test. Worsening of the finger-pointing test with the eyes closed is another feature of sensory ataxia. Also, when patients are standing with arms and hands extended toward the physician, if the eyes are closed, the patients' fingers tend to "fall down" and then be restored to the horizontal extended position by sudden muscular contractions (the "ataxic hand").

Vestibular

The term vestibular ataxia is used to indicate ataxia due to dysfunction of the vestibular system, which in acute and unilateral cases is associated with prominent vertigo, nausea, and vomiting. In slow-onset, chronic bilateral cases of vestibular dysfunction, these characteristic manifestations may be absent, and dysequilibrium may be the sole presentation.

Causes

The three types of ataxia have overlapping causes, so can either coexist or occur in isolation. Cerebellar ataxia can have many causes despite normal neuroimaging.

Focal lesions

Any type of focal lesion of the central nervous system (such as stroke, brain tumor, multiple sclerosis, inflammatory [such as sarcoidosis], and "chronic lymphocytyc inflammation with pontine perivascular enhancement responsive to steroids syndrome" [CLIPPERS[14]]) will cause the type of ataxia corresponding to the site of the lesion: cerebellar if in the cerebellum; sensory if in the dorsal spinal cord...to include cord compression by thickened ligamentum flavum or stenosis of the boney spinal canal...(and rarely in the thalamus or parietal lobe); or vestibular if in the vestibular system (including the vestibular areas of the cerebral cortex).

Exogenous substances

Exogenous substances that cause ataxia mainly do so because they have a depressant effect on central nervous system function. The most common example is ethanol (alcohol), which is capable of causing reversible cerebellar and vestibular ataxia. Other examples include various prescription drugs (e.g. most antiepileptic drugs have cerebellar ataxia as a possible adverse effect), Lithium level over 1.5mEq/L, synthetic cannabinoid HU-211 ingestion[15] and various other medical and recreational drugs (e.g. ketamine, PCP or dextromethorphan, all of which are NMDA receptor antagonists that produce a dissociative state at high doses). A further class of pharmaceuticals which can cause short term ataxia, especially in high doses, are benzodiazepines.[16][17] Exposure to high levels of methylmercury, through consumption of fish with high mercury concentrations, is also a known cause of ataxia and other neurological disorders.[18]

Radiation

Ataxia can be induced as a result of severe acute radiation poisoning with an absorbed dose of more than 30 grays.

Vitamin B12 deficiency

Vitamin B12 deficiency may cause, among several neurological abnormalities, overlapping cerebellar and sensory ataxia.

Hypothyroidism

Symptoms of neurological dysfunction may be the presenting feature in some patients with hypothyroidism. These include reversible cerebellar ataxia, dementia, peripheral neuropathy, psychosis and coma. Most of the neurological complications improve completely after thyroid hormone replacement therapy.[19][20]

Isolated sensory ataxia

Peripheral neuropathies may cause generalised or localised sensory ataxia (e.g. a limb only) depending on the extent of the neuropathic involvement. Spinal disorders of various types may cause sensory ataxia from the lesioned level below, when they involve the dorsal columns.[21][22][23]

Non-hereditary cerebellar degeneration

Non-hereditary causes of cerebellar degeneration include chronic alcohol abuse, head injury, paraneoplastic and non-paraneoplastic autoimmune ataxia,[24][25][26] high altitude cerebral oedema, coeliac disease, normal pressure hydrocephalus and infectious or post-infectious cerebellitis.

Hereditary ataxias

Ataxia may depend on hereditary disorders consisting of degeneration of the cerebellum or of the spine; most cases feature both to some extent, and therefore present with overlapping cerebellar and sensory ataxia, even though one is often more evident than the other. Hereditary disorders causing ataxia include autosomal dominant ones such as spinocerebellar ataxia, episodic ataxia, and dentatorubropallidoluysian atrophy, as well as autosomal recessive disorders such as Friedreich's ataxia (sensory and cerebellar, with the former predominating) and Niemann Pick disease, ataxia-telangiectasia (sensory and cerebellar, with the latter predominating), and abetalipoproteinaemia. An example of X-linked ataxic condition is the rare fragile X-associated tremor/ataxia syndrome or FXTAS.

Arnold–Chiari malformation

Arnold–Chiari malformation is a malformation of the brain. It consists of a downward displacement of the cerebellar tonsils and the medulla through the foramen magnum, sometimes causing hydrocephalus as a result of obstruction of cerebrospinal fluid outflow.

Succinic semialdehyde dehydrogenase deficiency

Succinic semialdehyde dehydrogenase deficiency is an autosomal-recessive gene disorder where mutations in the ALDH5A1 gene results in the accumulation of gamma-Hydroxybutyric acid (GHB) in the body. GHB accumulates in the nervous system and can cause ataxia as well as other neurological dysfunction.[27]

Wilson's disease

Wilson's disease is an autosomal-recessive gene disorder whereby an alteration of the ATP7B gene results in an inability to properly excrete copper from the body.[28] Copper accumulates in the nervous system and liver and can cause ataxia as well as other neurological and organ impairments.[29]

Gluten ataxia

Gluten ataxia is an autoimmune disease triggered by the ingestion of gluten.[30][31] Early diagnosis and treatment with a gluten-free diet can improve ataxia and prevent its progression. The effectiveness of the treatment depends on the elapsed time from the onset of the ataxia until diagnosis, because the death of neurons in the cerebellum as a result of gluten exposure is irreversible.[30][32] It accounts for 40% of ataxias of unknown origin and 15% of all ataxias.[32] Less than 10% of people with gluten ataxia present any gastrointestinal symptom, yet about 40% have intestinal damage.[30][32] In some cases, the immune ataxia remains of unknown origin and lacks biomarkers. This entity is called primary auto-immune ataxia (PACA).[33]

Potassium pump

Malfunction of the sodium-potassium pump may be a factor in some ataxias. The Na+
-K+
 pump has been shown to control and set the intrinsic activity mode of cerebellar Purkinje neurons.[34] This suggests that the pump might not simply be a homeostatic, "housekeeping" molecule for ionic gradients; but could be a computational element in the cerebellum and the brain.[35] Indeed, an ouabain block of Na+
-K+
 pumps in the cerebellum of a live mouse results in it displaying ataxia and dystonia.[36] Ataxia is observed for lower ouabain concentrations, dystonia is observed at higher ouabain concentrations.

Cerebellar ataxia associated with anti-GAD antibodies

Antibodies against the enzyme glutamic acid decarboxylase (GAD: enzyme changing glutamate into GABA) cause cerebellar deficits.[37] The antibodies impair motor learning and cause behavioral deficits.[38] GAD antibodies related ataxia is part of the group called immune-mediated cerebellar ataxias.[39] The antibodies induce a synaptopathy.[40]

Diagnosis

  • Imaging studies - A CT scan or MRI of the brain might help determine potential causes. An MRI can sometimes show shrinkage of the cerebellum and other brain structures in people with ataxia. It may also show other treatable findings, such as a blood clot or benign tumour, that could be pressing on the cerebellum.
  • Lumbar puncture (spinal tap) - A needle is inserted into the lower back (lumbar region) between two lumbar vertebrae to obtain a sample of cerebrospinal fluid for testing.
  • Genetic testing - Determines whether the mutation that causes one of the hereditary ataxic conditions is present. Tests are available for many but not all of the hereditary ataxias.

Treatment

The treatment of ataxia and its effectiveness depend on the underlying cause. Treatment may limit or reduce the effects of ataxia, but it is unlikely to eliminate them entirely. Recovery tends to be better in individuals with a single focal injury (such as stroke or a benign tumour), compared to those who have a neurological degenerative condition.[41] A review of the management of degenerative ataxia was published in 2009.[42] A small number of rare conditions presenting with prominent cerebellar ataxia are amenable to specific treatment and recognition of these disorders is critical. Diseases include vitamin E deficiency, abetalipoproteinemia, cerebrotendinous xanthomatosis, Niemann–Pick type C disease, Refsum's disease, glucose transporter type 1 deficiency, episodic ataxia type 2, gluten ataxia, glutamic acid decarboxylase ataxia.[43] Novel therapies target the RNA defects associated with cerebellar disorders, using in particular anti-sense oligonucleotides.[44]

The movement disorders associated with ataxia can be managed by pharmacological treatments and through physical therapy and occupational therapy to reduce disability.[45] Some drug treatments that have been used to control ataxia include: 5-hydroxytryptophan (5-HTP), idebenone, amantadine, physostigmine, L-carnitine or derivatives, trimethoprim/sulfamethoxazole, vigabatrin, phosphatidylcholine, acetazolamide, 4-aminopyridine, buspirone, and a combination of coenzyme Q10 and vitamin E.[42]

Physical therapy requires a focus on adapting activity and facilitating motor learning for retraining specific functional motor patterns.[46] A recent systematic review suggested that physical therapy is effective, but there is only moderate evidence to support this conclusion.[47] The most commonly used physical therapy interventions for cerebellar ataxia are vestibular habituation, Frenkel exercises, proprioceptive neuromuscular facilitation (PNF), and balance training; however, therapy is often highly individualized and gait and coordination training are large components of therapy.

Current research suggests that, if a person is able to walk with or without a mobility aid, physical therapy should include an exercise program addressing five components: static balance, dynamic balance, trunk-limb coordination, stairs, and contracture prevention. Once the physical therapist determines that the individual is able to safely perform parts of the program independently, it is important that the individual be prescribed and regularly engage in a supplementary home exercise program that incorporates these components to further improve long term outcomes. These outcomes include balance tasks, gait, and individual activities of daily living. While the improvements are attributed primarily to changes in the brain and not just the hip or ankle joints, it is still unknown whether the improvements are due to adaptations in the cerebellum or compensation by other areas of the brain.[46]

Decomposition, simplification, or slowing of multijoint movement may also be an effective strategy that therapists may use to improve function in patients with ataxia.[48] Training likely needs to be intense and focused—as indicated by one study performed with stroke patients experiencing limb ataxia who underwent intensive upper limb retraining.[49] Their therapy consisted of constraint-induced movement therapy which resulted in improvements of their arm function.[49] Treatment should likely include strategies to manage difficulties with everyday activities such as walking. Gait aids (such as a cane or walker) can be provided to decrease the risk of falls associated with impairment of balance or poor coordination. Severe ataxia may eventually lead to the need for a wheelchair. To obtain better results, possible coexisting motor deficits need to be addressed in addition to those induced by ataxia. For example, muscle weakness and decreased endurance could lead to increasing fatigue and poorer movement patterns.

There are several assessment tools available to therapists and health care professionals working with patients with ataxia. The International Cooperative Ataxia Rating Scale (ICARS) is one of the most widely used and has been proven to have very high reliability and validity.[50] Other tools that assess motor function, balance and coordination are also highly valuable to help the therapist track the progress of their patient, as well as to quantify the patient's functionality. These tests include, but are not limited to:

Other uses

The term "ataxia" is sometimes used in a broader sense to indicate lack of coordination in some physiological process. Examples include optic ataxia (lack of coordination between visual inputs and hand movements, resulting in inability to reach and grab objects) and ataxic respiration (lack of coordination in respiratory movements, usually due to dysfunction of the respiratory centres in the medulla oblongata). Optic ataxia may be caused by lesions to the posterior parietal cortex, which is responsible for combining and expressing positional information and relating it to movement. Outputs of the posterior parietal cortex include the spinal cord, brain stem motor pathways, pre-motor and pre-frontal cortex, basal ganglia and the cerebellum. Some neurons in the posterior parietal cortex are modulated by intention. Optic ataxia is usually part of Balint's syndrome, but can be seen in isolation with injuries to the superior parietal lobule, as it represents a disconnection between visual-association cortex and the frontal premotor and motor cortex.[54]

See also

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Hafiz, S; De Jesus, O (January 2020). "Ataxia". PMID 32965955. {{cite journal}}: Cite journal requires |journal= (help)
  2. ↑ Caplan, Louis R.; Gijn, Jan van (2012). Stroke Syndromes, 3ed. Cambridge University Press. p. 21. ISBN 978-1-139-53663-9. Archived from the original on 2021-08-27. Retrieved 2021-01-16.
  3. ↑ "Ataxia - Symptoms & Causes". Mayo Clinic. 3 June 2020. Archived from the original on 5 August 2020. Retrieved 10 August 2020.
  4. 1 2 3 4 5 6 7 Schmahmann JD (2004). "Disorders of the cerebellum: ataxia, dysmetria of thought, and the cerebellar cognitive affective syndrome". The Journal of Neuropsychiatry and Clinical Neurosciences. 16 (3): 367–78. doi:10.1176/jnp.16.3.367. PMID 15377747.
  5. ↑ Fredericks CM (1996). "Disorders of the Cerebellum and Its Connections" (PDF). In Saladin LK, Fredericks CM (eds.). Pathophysiology of the motor systems: principles and clinical presentations. Philadelphia: F.A. Davis. ISBN 0-8036-0093-3. Retrieved 6 May 2012.
  6. ↑ Tada M, Nishizawa M, Onodera O (August 2015). "Redefining cerebellar ataxia in degenerative ataxias: lessons from recent research on cerebellar systems". Journal of Neurology, Neurosurgery, and Psychiatry. 86 (8): 922–8. doi:10.1136/jnnp-2013-307225. PMID 25637456. S2CID 20887739.
  7. ↑ Manto M, Godaux E, Jacquy J (January 1994). "Cerebellar hypermetria is larger when the inertial load is artificially increased". Annals of Neurology. 35 (1): 45–52. doi:10.1002/ana.410350108. PMID 8285591.
  8. ↑ Bastian AJ, Zackowski KM, Thach WT (May 2000). "Cerebellar ataxia: torque deficiency or torque mismatch between joints?". Journal of Neurophysiology. 83 (5): 3019–30. doi:10.1152/jn.2000.83.5.3019. PMID 10805697.
  9. 1 2 Blumenfeld H (2002). Neuroanatomy through clinical cases. Sunderland, Mass: Sinauer. pp. 670–671. ISBN 0-87893-060-4.
  10. ↑ Fonteyn EM, Schmitz-Hübsch T, Verstappen CC, Baliko L, Bloem BR, Boesch S, et al. (June 2010). "Falls in spinocerebellar ataxias: Results of the EuroSCA Fall Study". Cerebellum. 9 (2): 232–9. doi:10.1007/s12311-010-0155-z. PMID 20157791.
  11. ↑ van de Warrenburg BP, Steijns JA, Munneke M, Kremer BP, Bloem BR (April 2005). "Falls in degenerative cerebellar ataxias". Movement Disorders. 20 (4): 497–500. doi:10.1002/mds.20375. PMID 15645525.
  12. 1 2 3 Schmitz TJ, O'Sullivan SB (2007). "Examination of Coordination". Physical rehabilitation. Philadelphia: F.A. Davis. pp. 193–225. ISBN 978-0-8036-1247-1.
  13. ↑ Manto M, Mariën P (2015). "Schmahmann's syndrome - identification of the third cornerstone of clinical ataxiology". Cerebellum & Ataxias. 2: 2. doi:10.1186/s40673-015-0023-1. PMC 4552302. PMID 26331045.
  14. ↑ Maenhoudt W, Ramboer K, Maqueda V (February 2016). "A Rare Cause of Dizziness and Gait Ataxia: CLIPPERS Syndrome". Journal of the Belgian Society of Radiology. 100 (1): 20. doi:10.5334/jbr-btr.997. PMC 6102946. PMID 30151443.
  15. ↑ "Inadvertent Ingestion of Marijuana --- Los Angeles, California, 2009". Archived from the original on 11 May 2011. Retrieved 3 September 2009.
  16. ↑ Browne TR (May 1976). "Clonazepam. A review of a new anticonvulsant drug". Archives of Neurology. 33 (5): 326–32. doi:10.1001/archneur.1976.00500050012003. PMID 817697.
  17. ↑ Gaudreault P, Guay J, Thivierge RL, Verdy I (1991). "Benzodiazepine poisoning. Clinical and pharmacological considerations and treatment". Drug Safety. 6 (4): 247–65. doi:10.2165/00002018-199106040-00003. PMID 1888441. S2CID 27619795.
  18. ↑ Díez S (2009). "Human health effects of methylmercury exposure". Reviews of Environmental Contamination and Toxicology. 198: 111–32. doi:10.1007/978-0-387-09647-6_3. ISBN 978-0-387-09646-9. PMID 19253038. {{cite journal}}: Cite journal requires |journal= (help)
  19. ↑ Victor M, Ropper AH, Adams RD, Samuels M (2009). Adams and Victor's Principles of Neurology (Ninth ed.). McGraw-Hill Medical. pp. 78–88. ISBN 978-0-07-149992-7.
  20. ↑ Pavan MR, Deepak M, Basavaprabhu A, Gupta A (2012). "Doctor i am swaying – An interesting case of ataxia". Journal of Clinical and Diagnostic Research. Archived from the original on 8 May 2014. Retrieved 2 May 2013.
  21. ↑ Spinazzi M, Angelini C, Patrini C (May 2010). "Subacute sensory ataxia and optic neuropathy with thiamine deficiency". Nature Reviews. Neurology. 6 (5): 288–93. doi:10.1038/nrneurol.2010.16. PMID 20308997. S2CID 12333200.
  22. ↑ Sghirlanzoni A, Pareyson D, Lauria G (June 2005). "Sensory neuron diseases". The Lancet. Neurology. 4 (6): 349–61. doi:10.1016/S1474-4422(05)70096-X. PMID 15907739. S2CID 35053543.
  23. ↑ Moeller JJ, Macaulay RJ, Valdmanis PN, Weston LE, Rouleau GA, Dupré N (September 2008). "Autosomal dominant sensory ataxia: a neuroaxonal dystrophy". Acta Neuropathologica. 116 (3): 331–6. doi:10.1007/s00401-008-0362-6. PMID 18347805. S2CID 22881684.
  24. ↑ Jarius S, Wildemann B (September 2015). "'Medusa-head ataxia': the expanding spectrum of Purkinje cell antibodies in autoimmune cerebellar ataxia. Part 1: Anti-mGluR1, anti-Homer-3, anti-Sj/ITPR1 and anti-CARP VIII". Journal of Neuroinflammation. 12 (1): 166. doi:10.1186/s12974-015-0356-y. PMC 4574226. PMID 26377085.
  25. ↑ Jarius S, Wildemann B (September 2015). "'Medusa head ataxia': the expanding spectrum of Purkinje cell antibodies in autoimmune cerebellar ataxia. Part 2: Anti-PKC-gamma, anti-GluR-delta2, anti-Ca/ARHGAP26 and anti-VGCC". Journal of Neuroinflammation. 12 (1): 167. doi:10.1186/s12974-015-0357-x. PMC 4574118. PMID 26377184.
  26. ↑ Jarius S, Wildemann B (September 2015). "'Medusa head ataxia': the expanding spectrum of Purkinje cell antibodies in autoimmune cerebellar ataxia. Part 3: Anti-Yo/CDR2, anti-Nb/AP3B2, PCA-2, anti-Tr/DNER, other antibodies, diagnostic pitfalls, summary and outlook". Journal of Neuroinflammation. 12 (1): 168. doi:10.1186/s12974-015-0358-9. PMC 4573944. PMID 26377319.
  27. ↑ Parviz M, Vogel K, Gibson KM, Pearl PL (November 2014). "Disorders of GABA metabolism: SSADH and GABA-transaminase deficiencies". Journal of Pediatric Epilepsy. 3 (4): 217–227. doi:10.3233/PEP-14097. PMC 4256671. PMID 25485164.
  28. ↑ Walshe JM. Clarke CE, Nicholl DJ (eds.). "Wilson's Disease" (PDF). Birmingham Movement Disorders Coursebook. Archived from the original (PDF) on 10 September 2011.
  29. ↑ Haldeman-Englert C. "Wilson's disease – PubMed Health". PubMed Health. Archived from the original on 27 July 2014.
  30. 1 2 3 Mitoma H, Adhikari K, Aeschlimann D, Chattopadhyay P, Hadjivassiliou M, Hampe CS, et al. (April 2016). "Consensus Paper: Neuroimmune Mechanisms of Cerebellar Ataxias". Cerebellum (Review). 15 (2): 213–32. doi:10.1007/s12311-015-0664-x. PMC 4591117. PMID 25823827.
  31. ↑ Sapone A, Bai JC, Ciacci C, Dolinsek J, Green PH, Hadjivassiliou M, et al. (February 2012). "Spectrum of gluten-related disorders: consensus on new nomenclature and classification". BMC Medicine (Review). 10: 13. doi:10.1186/1741-7015-10-13. PMC 3292448. PMID 22313950.
  32. 1 2 3 Hadjivassiliou M, Sanders DD, Aeschlimann DP (2015). "Gluten-related disorders: gluten ataxia". Digestive Diseases (Review). 33 (2): 264–8. doi:10.1159/000369509. PMID 25925933. S2CID 207673823.
  33. ↑ Hadjivassiliou M, Graus F, Honnorat J, Jarius S, Titulaer M, Manto M, et al. (August 2020). "Diagnostic Criteria for Primary Autoimmune Cerebellar Ataxia-Guidelines from an International Task Force on Immune-Mediated Cerebellar Ataxias". Cerebellum. 19 (4): 605–610. doi:10.1007/s12311-020-01132-8. PMC 7351847. PMID 32328884.
  34. ↑ Forrest MD, Wall MJ, Press DA, Feng J (December 2012). "The sodium-potassium pump controls the intrinsic firing of the cerebellar Purkinje neuron". PLOS One. 7 (12): e51169. Bibcode:2012PLoSO...751169F. doi:10.1371/journal.pone.0051169. PMC 3527461. PMID 23284664.
  35. ↑ Forrest MD (December 2014). "The sodium-potassium pump is an information processing element in brain computation". Frontiers in Physiology. 5 (472): 472. doi:10.3389/fphys.2014.00472. PMC 4274886. PMID 25566080.
  36. ↑ Calderon DP, Fremont R, Kraenzlin F, Khodakhah K (March 2011). "The neural substrates of rapid-onset Dystonia-Parkinsonism". Nature Neuroscience. 14 (3): 357–65. doi:10.1038/nn.2753. PMC 3430603. PMID 21297628.
  37. ↑ Mitoma H, Manto M, Hampe CS (2017). "Pathogenic Roles of Glutamic Acid Decarboxylase 65 Autoantibodies in Cerebellar Ataxias". Journal of Immunology Research. 2017: 2913297. doi:10.1155/2017/2913297. PMC 5366212. PMID 28386570.
  38. ↑ Manto M, Honnorat J, Hampe CS, Guerra-Narbona R, López-Ramos JC, Delgado-García JM, et al. (2015). "Disease-specific monoclonal antibodies targeting glutamate decarboxylase impair GABAergic neurotransmission and affect motor learning and behavioral functions". Frontiers in Behavioral Neuroscience. 9: 78. doi:10.3389/fnbeh.2015.00078. PMC 4375997. PMID 25870548.
  39. ↑ Mitoma H, Manto M, Hampe CS (2019). "Immune-mediated Cerebellar Ataxias: Practical Guidelines and Therapeutic Challenges". Current Neuropharmacology. 17 (1): 33–58. doi:10.2174/1570159X16666180917105033. PMC 6341499. PMID 30221603.
  40. ↑ Mitoma H, Honnorat J, Yamaguchi K, Manto M (July 2020). "Fundamental Mechanisms of Autoantibody-Induced Impairments on Ion Channels and Synapses in Immune-Mediated Cerebellar Ataxias". International Journal of Molecular Sciences. 21 (14): E4936. doi:10.3390/ijms21144936. PMC 6341499. PMID 32668612.
  41. ↑ Morton SM, Bastian AJ (December 2009). "Can rehabilitation help ataxia?". Neurology. 73 (22): 1818–9. doi:10.1212/WNL.0b013e3181c33b21. PMID 19864635. S2CID 5481310.
  42. 1 2 Trujillo-Martín MM, Serrano-Aguilar P, Monton-Alvarez F, Carrillo-Fumero R (June 2009). "Effectiveness and safety of treatments for degenerative ataxias: a systematic review". Movement Disorders. 24 (8): 1111–24. doi:10.1002/mds.22564. PMID 19412936.
  43. ↑ Ramirez-Zamora A, Zeigler W, Desai N, Biller J (April 2015). "Treatable causes of cerebellar ataxia". Movement Disorders. 30 (5): 614–23. doi:10.1002/mds.26158. PMID 25757427.
  44. ↑ Manto M, Gandini J, Feil K, Strupp M (February 2020). "Cerebellar ataxias: an update". Current Opinion in Neurology. 33 (1): 150–160. doi:10.1097/WCO.0000000000000774. PMID 31789706.
  45. ↑ Perlman SL (November 2006). "Ataxias". Clinics in Geriatric Medicine. 22 (4): 859–77, vii. doi:10.1016/j.cger.2006.06.011. PMID 17000340.
  46. 1 2 Ilg W, Synofzik M, Brötz D, Burkard S, Giese MA, Schöls L (December 2009). "Intensive coordinative training improves motor performance in degenerative cerebellar disease". Neurology. 73 (22): 1823–30. doi:10.1212/WNL.0b013e3181c33adf. PMID 19864636. S2CID 2087750.
  47. ↑ Martin CL, Tan D, Bragge P, Bialocerkowski A (January 2009). "Effectiveness of physiotherapy for adults with cerebellar dysfunction: a systematic review". Clinical Rehabilitation. 23 (1): 15–26. doi:10.1177/0269215508097853. PMID 19114434. S2CID 25458915.
  48. ↑ Bastian AJ (June 1997). "Mechanisms of ataxia". Physical Therapy. 77 (6): 672–5. doi:10.1093/ptj/77.6.672. PMID 9184691.
  49. 1 2 Richards L, Senesac C, McGuirk T, Woodbury M, Howland D, Davis S, Patterson T (2008). "Response to intensive upper extremity therapy by individuals with ataxia from stroke". Topics in Stroke Rehabilitation. 15 (3): 262–71. doi:10.1310/tsr1503-262. PMID 18647730. S2CID 207260777.
  50. ↑ Schmitz-Hübsch T, Tezenas du Montcel S, Baliko L, Boesch S, Bonato S, Fancellu R, et al. (May 2006). "Reliability and validity of the International Cooperative Ataxia Rating Scale: a study in 156 spinocerebellar ataxia patients". Movement Disorders. 21 (5): 699–704. doi:10.1002/mds.20781. PMID 16450347.
  51. ↑ Schmitz-Hübsch T, du Montcel ST, Baliko L, Berciano J, Boesch S, Depondt C, et al. (June 2006). "Scale for the assessment and rating of ataxia: development of a new clinical scale". Neurology. 66 (11): 1717–20. doi:10.1212/01.wnl.0000219042.60538.92. PMID 16769946. S2CID 24069559.
  52. 1 2 Notermans NC, van Dijk GW, van der Graaf Y, van Gijn J, Wokke JH (January 1994). "Measuring ataxia: quantification based on the standard neurological examination". Journal of Neurology, Neurosurgery, and Psychiatry. 57 (1): 22–6. doi:10.1136/jnnp.57.1.22. PMC 485035. PMID 8301300.
  53. ↑ "OPETA: Neurologic Examination". Online physical exam teaching assistant. The UF College of Medicine Harrell Center. Archived from the original on 18 March 2012. Retrieved 7 May 2012.
  54. ↑ Vallar G (July 2007). "Spatial neglect, Balint-Homes' and Gerstmann's syndrome, and other spatial disorders". CNS Spectrums. 12 (7): 527–36. doi:10.1017/S1092852900021271. PMID 17603404.
Classification
This article is issued from Offline. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.