Ataxias cerebelares não-progressivas e lesão cerebelar aguda prévia indeterminada: uma condição clínica misteriosa

Pinto, Wladimir Bocca Vieira de Rezende; Pedroso, José Luiz; Souza, Paulo Victor Sgobbi de; Albuquerque, Marcus Vinícius Cristino de; Barsottini, Orlando Graziani Povoas

doi:10.1590/0004-282X20150119

Wladimir Bocca Vieira de Rezende Pinto

Universidade Federal de São Paulo, Divisão de Neurologia Geral e Unidade de Ataxia, Departamento de Neurologia e Neurocirurgia, Sao Paulo SP, Brazil

José Luiz Pedroso

Universidade Federal de São Paulo, Divisão de Neurologia Geral e Unidade de Ataxia, Departamento de Neurologia e Neurocirurgia, Sao Paulo SP, Brazil

Paulo Victor Sgobbi de Souza

Universidade Federal de São Paulo, Divisão de Neurologia Geral e Unidade de Ataxia, Departamento de Neurologia e Neurocirurgia, Sao Paulo SP, Brazil

Marcus Vinícius Cristino de Albuquerque

Universidade Federal de São Paulo, Divisão de Neurologia Geral e Unidade de Ataxia, Departamento de Neurologia e Neurocirurgia, Sao Paulo SP, Brazil

Orlando Graziani Povoas Barsottini

Universidade Federal de São Paulo, Divisão de Neurologia Geral e Unidade de Ataxia, Departamento de Neurologia e Neurocirurgia, Sao Paulo SP, Brazil

Correspondence: José Luiz Pedroso; UNIFESP, Unidade de Ataxia, Departamento de Neurologia e Neurocirurgia; Rua Pedro de Toledo, 650; 04023-900 São Paulo SP, Brasil; E-mail: jlpedroso.neuro@gmail.com

Conflict of interests: There is no conflict of interest to declare.

Figuras (1)
Tabelas (3)

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Figure
Neuroimaging findings from patients 1, 2, 3 and 5, with variable degrees of pure cerebellar atrophy (Patient 2, 1B; Patient 3, 1C; Patient 5, 1D) and olivopontocerebellar atrophy (Patient 1, 1A).

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Table 1
Main differential diagnosis of acute cerebellar ataxia⁷7 .Steinlin M, Zangger B, Boltshauser E. Non-progressive congenital ataxia with or without cerebellar hypoplasia: a review of 34 subjects. Dev Med Child Neurol. 1998;40(3):148-54. doi:10.1111/j.1469-8749.1998.tb15438.x,⁸8 .Steinlin M. Non-progressive congenital ataxias. Brain Dev. 1998;20(4):199-208. doi:10.1016/S0387-7604(98)00019-9,⁹9 .Esscher E, Flodmark O, Hagberg G, Hagberg B. Non-progressive ataxia: origins, brain pathology and impairments in 78 swedish children. Dev Med Child Neurol. 1996;38(4):285-96. doi:10.1111/j.1469-8749.1996.tb12095.x,¹⁴14 .de Bot ST, Willemsen MA, Vermeer S, Kremer HP, van de Warrenburg BP. Reviewing the genetic causes of spastic-ataxias. Neurology. 2012;79(14):1507-14. doi:10.1212/WNL.0b013e31826d5fb0,¹⁵15 .Eirís-Puñal J, Gómez-Lado C, Castro-Gago M. [Non-progressive congenital ataxias]. Rev Neurol. 2006;43(10):621-9. Spanish.,¹⁶16 .van de Warrenburg BP, van Gaalen J, Boesch S, Burgunder JM, Dürr A, Giunti P et al. EFNS/ENS Consensus on the diagnosis and management of chronic ataxias in adulthood. Eur J Neurol. 2014;21(4):552-62. doi:10.1111/ene.12341,¹⁷17 .Yapici Z, Eraksoy M. Non-progressive congenital ataxia with cerebellar hypoplasia in three families. Acta Paediatr. 2005;94(2):248-53. doi:10.1080/08035250410022413,¹⁸18 .Ramaekers VT, Heimann G, Reul J, Thron A, Jaeken J. Genetic disorders and cerebellar structural abnormalities in childhood. Brain. 1997;120(10):1739-51. doi:10.1093/brain/120.10.1739,¹⁹19 .García-Cazorla A, Wolf NI, Serrano M, Pérez-Dueñas B, Pineda M, Campistol J et al. Inborn errors of metabolism and motor disturbances in children. J Inherit Metab Dis. 2009;32(5):618-29. doi:10.1007/s10545-009-1194-9,²⁰20 .Klockgether T. Sporadic ataxia with adult onset: classification and diagnostic criteria. Lancet Neurol. 2010;9(1):94-104. doi:10.1016/S1474-4422(09)70305-9,²¹21 .Thevenon J, Lopez E, Keren B, et al. Intragenic CAMTA1 rearrangements cause non-progressive congenital ataxia with or without intellectual disability. J Med Genet. 2012;49(6):400-8. doi:10.1136/jmedgenet-2012-100856,²²22 .Poretti A, Wolf NI, Boltshauser E. Differential diagnosis of cerebellar atrophy in childhood. Eur J Paediatr Neurol. 2008;12(3):155-67. doi:10.1016/j.ejpn.2007.07.010.

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Table 2
Clinical profile of adult patients with non-progressive cerebellar ataxia.

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Table 3
Main differential diagnosis of non-progressive cerebellar ataxia⁷7 .Steinlin M, Zangger B, Boltshauser E. Non-progressive congenital ataxia with or without cerebellar hypoplasia: a review of 34 subjects. Dev Med Child Neurol. 1998;40(3):148-54. doi:10.1111/j.1469-8749.1998.tb15438.x,⁸8 .Steinlin M. Non-progressive congenital ataxias. Brain Dev. 1998;20(4):199-208. doi:10.1016/S0387-7604(98)00019-9,⁹9 .Esscher E, Flodmark O, Hagberg G, Hagberg B. Non-progressive ataxia: origins, brain pathology and impairments in 78 swedish children. Dev Med Child Neurol. 1996;38(4):285-96. doi:10.1111/j.1469-8749.1996.tb12095.x,¹⁴14 .de Bot ST, Willemsen MA, Vermeer S, Kremer HP, van de Warrenburg BP. Reviewing the genetic causes of spastic-ataxias. Neurology. 2012;79(14):1507-14. doi:10.1212/WNL.0b013e31826d5fb0,¹⁵15 .Eirís-Puñal J, Gómez-Lado C, Castro-Gago M. [Non-progressive congenital ataxias]. Rev Neurol. 2006;43(10):621-9. Spanish.,¹⁶16 .van de Warrenburg BP, van Gaalen J, Boesch S, Burgunder JM, Dürr A, Giunti P et al. EFNS/ENS Consensus on the diagnosis and management of chronic ataxias in adulthood. Eur J Neurol. 2014;21(4):552-62. doi:10.1111/ene.12341,¹⁷17 .Yapici Z, Eraksoy M. Non-progressive congenital ataxia with cerebellar hypoplasia in three families. Acta Paediatr. 2005;94(2):248-53. doi:10.1080/08035250410022413,¹⁸18 .Ramaekers VT, Heimann G, Reul J, Thron A, Jaeken J. Genetic disorders and cerebellar structural abnormalities in childhood. Brain. 1997;120(10):1739-51. doi:10.1093/brain/120.10.1739,¹⁹19 .García-Cazorla A, Wolf NI, Serrano M, Pérez-Dueñas B, Pineda M, Campistol J et al. Inborn errors of metabolism and motor disturbances in children. J Inherit Metab Dis. 2009;32(5):618-29. doi:10.1007/s10545-009-1194-9,²⁰20 .Klockgether T. Sporadic ataxia with adult onset: classification and diagnostic criteria. Lancet Neurol. 2010;9(1):94-104. doi:10.1016/S1474-4422(09)70305-9,²¹21 .Thevenon J, Lopez E, Keren B, et al. Intragenic CAMTA1 rearrangements cause non-progressive congenital ataxia with or without intellectual disability. J Med Genet. 2012;49(6):400-8. doi:10.1136/jmedgenet-2012-100856,²²22 .Poretti A, Wolf NI, Boltshauser E. Differential diagnosis of cerebellar atrophy in childhood. Eur J Paediatr Neurol. 2008;12(3):155-67. doi:10.1016/j.ejpn.2007.07.010.

Differential diagnosis of acute cerebellar ataxia
I. Inflammatory postinfectious disorders
II. Inherited neurometabolic disorders (frequently intermittent or recurrent)
Maple syrup urine disease, Hartnup disease,SLC19A3 gene mutation, GLUT1 deficiency, partial biotinidase deficiency, pyruvate-dehydrogenase deficiency, NARP syndrome, Leigh’s syndrome, pyruvate carboxylase deficiency type C, organic acidemias/acidurias (urocanic, isovaleric, propionic and methylmalonic), urea cycle disorders (carbamoylphosphate-synthetase deficiency, ornithine-transcarbamoilase deficiency, arginase deficiency, argininosuccinate synthethase deficiency), carnitine acethyltransferase deficiency, other aminoacidopathies
III. Infectious disorders
Acute infectious cerebellitis and rhombencephalitis (e.g. Chickenpox virus, Epstein-Barr virus)
IV. Cerebrovascular disorders
Stroke (cerebellar infarction or hemorrhage), dural sinus thrombosis
V. Ion channel disorders
Episodic ataxias
VI. Miscellaneous
Drug-induced, demyelinating disorders (multiple sclerosis, acute disseminated encephalomyelitis), Paraneoplastic (rare)

Patients	1	2	3	4	5
Age at evaluation	38 years	13 years	38 years	48 years	52 years
Gender	F	M	F	F	F
Age of onset	14 years	13 years	22 years	11 years	44 years
First complaint	GI	GI (intermittent)	GI, head tremor, slurred speech	GI, head tremor, slurred speech	GI
Duration of first complaints	Minutes	1 month	5 days	5 days	10 days
Type of cerebellar ataxia	Axial, appendicular	Appendicular	Appendicular	Axial, appendicular	Appendicular
Other neurological findings	Mild dysarthria	Mild dysarthria, headache, diplopia, Achilles clonus	Moderate dysarthria, headache	Mild dysarthria, left VI cranial nerve palsy (congenital)	Mild dysarthria, distal lower limbs hypoesthesia
Medical history	Constipation	Scoliosis	No	No	Constipation
Neurological family history	Brother with cerebral palsy	Brother with seizures since 13-year-old	No	No	No
Abnormal neuroimaging findings	Moderate OPCA	Mild CA	Mild CA	Mild to moderate CA	Mild OPCA
SARA score	10	10	8	8	10
ICARS score	33	33	31	40	65

Differential diagnosis of non-progressive cerebellar ataxia
I. Cerebellar and posterior fossa congenital malformations (including midbrain-hindbrain developmental malformations) – most with infancy-onset
Hypoplasia of the vermis and/or cerebellar hemispheres, Pontocerebellar hypoplasia, Dandy-Walker syndrome Syndromic complex congenital malformations with cerebellar or pontocerebellar hypoplasia or dysgenesis (i.e. Joubert syndrome, Gomez-Lopez-Hernandez syndrome, among others)
II. Non-progressive congenital cerebellar ataxias – infancy-onset
Cerebellar hypoplasia of the granular cell layer Dysequilibrium syndrome (VLDLR-associated cerebellar hypoplasia) Congenital granuloprival hypoplasia of cerebellar and hippocampal cortex Syndromic congenital non-progressive cerebellar ataxias (i.e. Gillespie syndrome, Autosomal recessive cerebellar hypoplasia and endosteal sclerosis, among others)
III. Chronic non-progressive encephalopathy – neonatal-onset
Including prenatal and perinatal aetiologies
IV. Inherited neurometabolic disorders – variable age at onset (most in infancy)
Congenital disorders of glycosylation (CDG) types Ia and Iq Succinic-semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria) Others: Mitochondrial disorders, Pyruvate dehydrogenase deficiency, GLUT1 deficiency syndrome
V. Spastic-ataxic syndromes and/or degenerative spinocerebellar ataxias
Early-onset cerebellar ataxia with retained tendon reflexes (Harding ataxia)
VI. Adult-onset sporadic cerebellar ataxias
Post-infectious and autoimmune cerebellar ataxia; toxic agents (i.e. drug abuse and addiction, drug exposure, environmental toxins)

[1] Correspondence: José Luiz Pedroso; UNIFESP, Unidade de Ataxia, Departamento de Neurologia e Neurocirurgia; Rua Pedro de Toledo, 650; 04023-900 São Paulo SP, Brasil; E-mail: jlpedroso.neuro@gmail.com

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Ataxias cerebelares não-progressivas e lesão cerebelar aguda prévia indeterminada: uma condição clínica misteriosa