Idiopathic very late-onset cerebellar ataxia: a Brazilian case series / Ataxia cerebellar idiopática com início muito tardio: uma série de casos brasileiros

ABSTRACTThe authors present a Brazilian case series of eight patients with idiopathic very-late onset (mean 75.5 years old) cerebellar ataxia, featuring predominantly gait ataxia, associated with cerebellar atrophy.Method: 26 adult patients with a diagnosis of idiopathic late onset cerebellar ataxia were analyzed in a Brazilian ataxia outpatient clinic and followed regularly over 20 years. Among them, 8 elderly patients were diagnosed as probable very late onset cerebellar ataxia. These patients were evaluated with neurological, ophthalmologic and Mini-Mental Status examinations, brain MRI, and EMG.Results: 62.5% of patients were males, mean age was 81.9 years-old, and mean age of onset was 75.5 years. Gait cerebellar ataxia was observed in all patients, as well as, cerebellar atrophy on brain MRI. Mild cognitive impairment and visual loss, due to macular degeneration, were observed in 50% of cases. Chorea was concomitantly found in 3 patients.Conclusion: We believe that this condition is similar the one described by Marie-Foix-Alajouanine presenting with mild dysarthria, associated with gait ataxia, and some patients had cognitive dysfunction and chorea.

RESUMOOs autores apresentam uma série de casos incluindo oito pacientes com ataxia cerebellar de início muito tardio (média de 75,5 anos de idade) apresentando ataxia de marcha, associada à atrofia cerebelar.Método: 26 pacientes adultos com diagnóstico de ataxia cerebelar de início tardio idiopática foram analisados ambulatorialmente e acompanhados regularmente ao longo de 20 anos. Destes, oito pacientes idosos foram diagnosticados como provável ataxia cerebelar início muito tardio. Os pacientes foram submetidos a um exame neurológico completo, avaliação cognitive e oftalmológica assim como ressonância magnética do cérebro e eletroneuromiografia tambem foram realizados.Resultados: 62,5% dos pacientes eram do sexo masculino, com idade média de 81,9 anos, com média de idade de início aos 75,5 anos. Ataxia cerebelar predominante de marcha foi observada em todos os pacientes, bem como, a atrofia cerebelar na ressonância magnética cerebral. Comprometimento cognitivo leve e perda visual, devido à degeneração macular, foram observados em 50% dos casos. Coréia foi encontrada em 3 pacientes.Conclusão: Acreditamos que esta condição é semelhante à descrita por Marie-Foix-Alajouanine apresentando disartria leve, associada a ataxia de marcha, disfunção cognitiva e coréia.

Idiopathic very late-onset cerebellar ataxia: a Brazilian case series.

UNLABELLED: The authors present a Brazilian case series of eight patients with idiopathic very-late onset (mean 75.5 years old) cerebellar ataxia, featuring predominantly gait ataxia, associated with cerebellar atrophy. METHOD: 26 adult patients with a diagnosis of idiopathic late onset cerebellar ataxia were analyzed in a Brazilian ataxia outpatient clinic and followed regularly over 20 years. Among them, 8 elderly patients were diagnosed as probable very late onset cerebellar ataxia. These patients were evaluated with neurological, ophthalmologic and Mini-Mental Status examinations, brain MRI, and EMG. RESULTS: 62.5% of patients were males, mean age was 81.9 years-old, and mean age of onset was 75.5 years. Gait cerebellar ataxia was observed in all patients, as well as, cerebellar atrophy on brain MRI. Mild cognitive impairment and visual loss, due to macular degeneration, were observed in 50% of cases. Chorea was concomitantly found in 3 patients. CONCLUSION: We believe that this condition is similar the one described by Marie-Foix-Alajouanine presenting with mild dysarthria, associated with gait ataxia, and some patients had cognitive dysfunction and chorea.

Hemichorea-Hemiballismus as the First Sign of Type 1b Diabetes During Adolescence and Its Recurrence in the Setting of Infection.

Chorea may be secondary to hyperosmolar nonketotic hyperglycemia, but such situation has rarely been described in adolescents, particularly as the initial and single manifestation of type 1 diabetes. We describe a case of a previously healthy 14-year-old girl with sudden onset of choreic movements on her left upper and lower limbs. Brain computed tomography (CT) and magnetic resonance imaging (MRI) revealed an area of hyperdensity/hyperintensity affecting the right striatum. Blood glucose was 349 mg/dL. Despite adequate glucose control, the involuntary movements persisted and haloperidol, later substituted with valproate, was prescribed, with satisfactory but not complete resolution of the chorea. In 2 other occasions, when the patient had an infection and subsequent hyperglycemia, the chorea relapsed. Although not common, hyperglycemia must be considered in the differential diagnosis of acute hemichorea-hemiballismus in children and adolescents, particularly because it is a potentially reversible cause.

Brain SPECT in Sydenham's chorea in remission.

BACKGROUND: Sydenham's chorea, a major manifestation of rheumatic fever, is characterized by chorea, behavioral changes, and cognitive dysfunction. Perfusion changes in the basal ganglia are the most frequent imaging findings observed in patients with Sydenham's chorea. METHODS: Twelve adult women with Sydenham's chorea in remission underwent brain single-photon emission computed tomography (SPECT). Their scans underwent a quantification process to evaluate the perfusion of Brodmann's areas of the frontal lobes and basal ganglia. The results were compared with the findings from a control group that was matched by age. RESULTS: A pattern of hyperperfusion in the left putamen was observed in the patient group (P = 0.02). No significant difference was observed in relation to other brain regions. CONCLUSIONS: The findings of brain SPECT suggest that perfusion abnormalities of the basal ganglia may persist even after the remission of abnormal movements in patients with Sydenham's chorea.

Huntington disease and Huntington disease-like in a case series from Brazil.

The aim of this study was to identify the relative frequency of Huntington's disease (HD) and HD-like (HDL) disorders HDL1, HDL2, spinocerebellar ataxia type 2 (SCA2), SCA17, dentatorubral-pallidoluysian degeneration (DRPLA), benign hereditary chorea, neuroferritinopathy and chorea-acanthocytosis (CHAC), in a series of Brazilian families. Patients were recruited in seven centers if they or their relatives presented at least chorea, besides other findings. Molecular studies of HTT, ATXN2, TBP, ATN1, JPH3, FTL, NKX2-1/TITF1 and VPS13A genes were performed. A total of 104 families were ascertained from 2001 to 2012: 71 families from South, 25 from Southeast and 8 from Northeast Brazil. There were 93 HD, 4 HDL2 and 1 SCA2 families. Eleven of 104 index cases did not have a family history: 10 with HD. Clinical characteristics were similar between HD and non-HD cases. In HD, the median expanded (CAG)n (range) was 44 (40-81) units; R(2) between expanded HTT and age-at-onset (AO) was 0.55 (p=0.0001, Pearson). HDL2 was found in Rio de Janeiro (2 of 9 families) and Rio Grande do Sul states (2 of 68 families). We detected HD in 89.4%, HDL2 in 3.8% and SCA2 in 1% of 104 Brazilian families. There were no cases of HDL1, SCA17, DRPLA, neuroferritinopathy, benign hereditary chorea or CHAC. Only six families (5.8%) remained without diagnosis.

Chorea in primary antiphospholipid syndrome is associated with rheumatic fever.

The aim of the study is to evaluate the frequency of chorea in a cohort of primary antiphospholipid syndrome (PAPS) patients and their possible clinical and laboratory associations. The records of 88 PAPS patients, fulfilling Sapporo criteria, followed up at the rheumatology outpatient clinic, were analyzed in order to determine the frequency of chorea. Risk factors for chorea, clinical manifestations, associated comorbidities, serologic features and treatment strategies were analyzed. Eighty-eight PAPS patients were evaluated. Mean age was 40.6 ± 11.1 years, and 91% of them were Caucasian and 91% women. Four (4.5%) patients with chorea were identified: 2 of them (50%) had only one chorea episode and 2 (50%) had recurrent chorea. All patients had chorea onset before PAPS diagnosis. Mean age, gender and ethnical distribution were comparable in groups with or without seizures (P > 0.05). Interestingly, the comparison of the 4 PAPS patients with chorea with those without this abnormality (n = 84) demonstrated a lower BMI [21.1 (18-24.2) vs. 27.5 (17.5-40.9) kg/m(2), P = 0.049] and frequency of venous events (0 vs. 63.1%, P = 0.023) in the first group. A higher frequency of rheumatic fever (75% vs. 0, P < 0.001) and thrombocytopenia (75 vs. 21.4%, P = 0.041) was observed in PAPS individuals with chorea. Both groups were alike regarding the other clinical APS manifestations, disease duration, risk factors for cerebrovascular diseases, use of drugs and antiphospholipid antibodies (P > 0.05). This study demonstrated that 4.5% of PAPS patients had chorea, predominately before PAPS diagnosis, and this neurological abnormality was associated with rheumatic fever and thrombocytopenia. These data reinforce the need for RF diagnosis in those PAPS patients with chorea.

[Hemiballism-hemichorea with non-ketotic hyperglycemia: movement disorder related to diabetes mellitus]. / Hemibalismo-hemicoreia em estado hiperglicêmico não cetótico: distúrbio do movimento associado ao diabetes melito.

Diabetes mellitus, especially when not under control, can lead to several neurological complications being the development of involuntary movements one of the rarest presentations. Nonketotic hyperglycemia in aged patients who present with ballismus-chorea movements and cerebral image alterations in computerized tomography (CT) and magnetic resonance constitute a syndrome of recent characterization and few cases in literature. We present a case of a 75 year-old male patient admitted with history of hemiballismus-hemichorea movements, hyperglycemia, glycated hemoglobin of 14.4% and CT with a hyperdense area in the topography of the right basal ganglia. After glycemic control, the neurological signs resolved completely and the initial hyperdense lesion disappeared.

Hemibalismo-hemicoreia em estado hiperglicêmico não cetótico: distúrbio do movimento associado ao diabetes melito / Hemiballism-hemichorea with non-ketotic hyperglycemia: movement disorder related to diabetes mellitus

O diabetes melito, especialmente quando descompensado, pode culminar em várias complicações neurológicas, sendo o desenvolvimento de movimentos involuntários uma das formas mais raras. O estado hiperglicêmico não cetótico em pacientes idosos, que se apresentam com movimentos tipo balismo-coreia associados a alterações nos exames de imagem cerebral (tomografia computadorizada e/ou ressonância magnética), constitui uma síndrome de caracterização recente e de poucos relatos na literatura. Apresentamos o caso de um paciente admitido com história de movimentos involuntários do tipo hemibalismo-hemicoreia à esquerda associado a estado hiperglicêmico com hemoglobina glicada de 14,4 por cento. O exame tomográfico de crânio revelou área hiperdensa em topografia de gânglios da base à direita. Após controle glicêmico adequado, houve melhora progressiva e recuperação do quadro neurológico, com desaparecimento completo da lesão hiperdensa inicial.

Diabetes mellitus, especially when not under control, can lead to several neurological complications being the development of involuntary movements one of the rarest presentations. Nonketotic hyperglycemia in aged patients who present with ballismus-chorea movements and cerebral image alterations in computerized tomography (CT) and magnetic resonance constitute a syndrome of recent characterization and few cases in literature. We present a case of a 75 year-old male patient admitted with history of hemiballismus-hemichorea movements, hyperglycemia, glycated hemoglobin of 14.4 percent and CT with a hyperdense area in the topography of the right basal ganglia. After glycemic control, the neurological signs resolved completely and the initial hyperdense lesion disappeared.

Monocyte dysfunction in Sydenham's chorea patients.

Until now, there are no conclusive data about the mechanisms involved in motor symptoms of Sydenham's chorea (SC). Taking into account the autoreactive antibody-mediated hypothesis of SC pathogenesis, the SC may be associated with uncontrolled immune mechanisms. Besides the antibody hypothesis, the innate immune system has been underappreciated. Hence, we evaluated the activation state of monocytes, cells that are precursors of macrophages, to characterize the inflammation profile of patients. We assessed the surface molecules CD80, CD86, and human leukocyte antigen DR expression in patients with SC by flow cytometry analysis. Our results showed a decreased CD14(+) (monocyte) frequency, with concomitant increased CD14(-) frequency inside monocyte population. Although monocyte population showed a decreased human leukocyte antigen DR and CD86 frequencies, the CD14(-) population showed an increased frequency of CD80(+) monocyte from SC compared with controls. These data suggest that monocytes showed a reduced costimulatory potential in SC.

Chorea-acanthocytosis: report of two Brazilian cases.

Chorea-acanthocytosis (ChAc) is a neurodegenerative disorder characterized by chorea, neuropsychiatric disturbances and acanthocytosis, caused by mutations of VPS13A. This gene produces the protein chorein which is absent in patients with ChAc on Western blot assay. We report the first two Brazilian patients with ChAc confirmed by chorein detection. Patient 1 is a 36-year-old man with chorea, epilepsy, myopathy, and suicidal ideation. Patient 2 is a 60-year-old woman with a 30 year history of psychiatric disturbances, epilepsy, choreic movements, and myopathy. Both patients had acanthocytosis, elevated creatine kinase (CK), and absence of chorein on Western blot analysis. The presence of chorea and neuropsychiatric disturbances associated with elevated CK levels, epilepsy, hyporeflexia, and acanthocytosis suggests the diagnosis of ChAc. Chorein assay of peripheral blood confirms the diagnosis.

Chorea-ballism as a manifestation of decompensated type 2 diabetes mellitus.

Chorea and ballism are movement disorders that result from a variety of conditions. Hyperglycemia is an unusual recognized cause of these movement disorders. We report 3 cases of new-onset chorea-ballism induced by nonketotic hyperglycemia in elderly patients, highlighting that chorea may be the first manifestation of undiagnosed decompensated diabetes mellitus.

Phenotypic variability of a distinct deletion in McLeod syndrome.

The X-linked McLeod neuroacanthocytosis syndrome strongly resembles Huntington's disease and has been reported in various countries world-wide. Herein, we report two Chilean brothers with predominant psychiatric features at disease onset including schizophrenia-like psychosis and obsessive compulsive disorder. Molecular genetic analysis revealed a small deletion in the XK gene (938-942delCTCTA), which has been already described in a North American patient of Anglo-Saxon descent and a Japanese family, presenting with seizures, muscle atrophy or chorea yet absence of psychiatric features. These findings argue against a founder effect and indicate a profound phenotypic variability associated with the 938-942delCTCTA deletion. Our report supports the inclusion of McLeod syndrome in the differential diagnosis of Huntington's disease as well as acute psychosis in male subjects.

Seminar on choreas.

Chorea is one of the major types of involuntary movement disorders originating from dysfunctional neuronal networks interconnecting the basal ganglia and frontal cortical motor areas. The syndrome is characterised by a continuous flow of random, brief, involuntary muscle contractions and can result from a wide variety of causes. Diagnostic work-up can be straightforward in patients with a positive family history of Huntington's disease or acute-onset hemichorea in patients with lacunar stroke, but it can be a challenging and complex task in rare autoimmune or genetic choreas. Principles of management focus on establishing an aetiological classification and, if possible, removal of the cause. Preventive strategies may be possible in Huntington's disease where genetic counselling plays a major part. In this review we summarise the current understanding of the neuroanatomy and pathophysiology of chorea, its major aetiological classes, and principles of diagnostic work-up and management.

UFMG Sydenham's chorea rating scale (USCRS): reliability and consistency.

Despite the renewed interest in Sydenham's chorea (SC) in recent years, there were no valid and reliable scales to rate the several signs and symptoms of patients with SC and related disorders. The Universidade Federal de Minas Gerais (UFMG) Sydenham's Chorea Rating Scale (USCRS) was designed to provide a detailed quantitative description of the performance of activities of daily living, behavioral abnormalities, and motor function of subjects with SC. The scale comprises 27 items and each one is scored from 0 (no symptom or sign) to 4 (severe disability or finding). Data from 84 subjects, aged 4.9 to 33.6 years, support the interrater reliability and internal consistency of the scale. The USCRS is a promising instrument for rating the clinical features of SC as well as their functional impact in children and adults.