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Being treatable, steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), or Hashimoto's encephalopathy, should be distinguished from untreatable conditions. Our patient was a previously healthy 89-year-old man, who presented with cognitive and balance deterioration over several months. His cerebrospinal fluid (CSF) examination was positive for protein 14-3-3 but no other test suggested Creutzfeldt-Jacob disease. His condition improved markedly, although not fully, with intravenous corticosteroids. In control CSF sampling, protein 14-3-3 was negative but a biomarker signature consistent with Alzheimer's disease was observed. SREAT should be considered also in the very elderly in case of subacute encephalopathy.
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The phenotype of juvenile Huntington's disease (HD) differs clearly from that of adult-onset HD, but information about differences between mid-age-onset HD and late-onset HD (LOHD) is scarce. A national cohort of 206 patients with adult-onset HD was identified using national registries and patient records. LOHD was defined as age ≥60 years at HD diagnosis. Genetic disease burden was assessed using CAG age product (CAP) score. LOHD comprised 25% of the adult-onset HD cohort giving a point prevalence of 2.38/100,000 in the Finnish population at least 60 years of age. The proportion of LOHD out of new HD diagnoses increased from 21% in 1991-2000 to 33% in 2001-2010. At the time of diagnosis, patients with LOHD had 10.4 units (95% CI 4.8-15.9; p = 0.0003) higher CAP scores, more severe motor impairment and slightly more severe functional impairment than that in patients with mid-age-onset HD. There was no difference in the rate of disease progression or survival between LOHD and mid-age-onset patients. The lifespans of deceased patients were shorter in mid-age-onset HD (p < 0.001) and LOHD (p = 0.002) than their life expectancies. Causes of death differed between the two patient groups (p = 0.025). LOHD comprises a quarter of Finnish HD patients and the proportion appears to be increasing. Our results did not reveal differences in the phenotype between mid-age-onset HD and LOHD, but prospective studies are needed.
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Edad de Inicio , Enfermedad de Huntington/epidemiología , Adulto , Factores de Edad , Anciano , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Finlandia/epidemiología , Humanos , Proteína Huntingtina/genética , Enfermedad de Huntington/genética , Enfermedad de Huntington/fisiopatología , Masculino , Persona de Mediana Edad , Estadísticas no Paramétricas , Repeticiones de Trinucleótidos/genéticaRESUMEN
Mutations in SNCA are rare causes of familial Parkinson's disease (PD). We have previously described a novel p.Ala53Glu mutation in 2 Finnish families. To assess this mutation's frequency among Finnish PD patients, we screened 110 PD patients (mean age-of-onset 60 years) from Western Finland by Sanger sequencing of the third coding exon of SNCA. In addition, a sample of 47 PD subjects (mean age-of-onset 53 years) originating from Southern and Eastern Finland were studied using next-generation sequencing covering SNCA. Only one new individual with the p.Ala53Glu mutation was identified, confirming that this mutation is a rare cause of PD in the Finnish population. To search for a possible common origin of the p.Ala53Glu mutation, haplotype analysis was conducted in 2 families and in a patient from a third family (6 affected subjects) using both STR markers and a genome-wide SNP array. The results show that patients with the p.Ala53Glu mutation share a haplotype spanning a minimum of 5.7 Mb suggesting a common founder.
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Efecto Fundador , Estudios de Asociación Genética , Mutación , Enfermedad de Parkinson/genética , alfa-Sinucleína/genética , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Exones/genética , Femenino , Finlandia , Haplotipos/genética , Humanos , Masculino , Persona de Mediana Edad , Población Blanca/genéticaRESUMEN
OBJECTIVE: To describe the clinical features and brain imaging findings of autosomal dominant Parkinson disease (PD) associated with a recently reported mutation in SNCA. METHODS: A Finnish family with PD in 3 successive generations, in accordance with an autosomal dominant inheritance pattern, was identified. We examined 2 available members of the family, the female proband and her daughter (both with early-onset PD), clinically and using dopamine transporter imaging ([(123)I]FP-CIT SPECT). A possible causative genetic defect was investigated by molecular genetic analyses. RESULTS: A heterozygous c.158C>A (p.A53E) point mutation in SNCA was revealed in both patients. The patients presented with PD clinically characterized by severe bradykinesia but with very little tremor and early onset of levodopa-induced dyskinesia. No cognitive decline or dysautonomic features have emerged during more than 5 years of follow-up. Both patients presented with a severe striatal binding defect in dopamine transporter SPECT imaging. CONCLUSIONS: The results of this observational study add evidence to the suggestion that the p.A53E mutation in SNCA is indeed pathogenic and results in autosomal dominant PD. Bradykinesia and early onset of levodopa-induced dyskinesia are the characteristic clinical features associated with the A53E mutation, but the patients did not exhibit dementia or dysautonomia. The [(123)I]FP-CIT SPECT findings indicated a profound, symmetric dopaminergic defect, in contrast to those observed in patients with idiopathic PD.
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OBJECT: To estimate the prevalence of Huntington's disease (HD) in Finland. METHODS: Persons diagnosed with HD from 1987 to 2010 were identified in the national registers and hospital records of the identified patients, and death certificates of the deceased subjects were obtained. Results of genetic analyses were obtained from the two national laboratories. RESULTS: Following the discovery of the Huntingtin gene (HTT), the rate of new diagnoses of HD has increased in Finland. We ascertained 207 patients with HD, 114 of whom were alive on 31 December, 2010 suggesting a minimum estimate of point prevalence of 2.12/100,000. The age at the time of diagnosis was 52.6 ± 12.1 years (mean ± standard deviation) and the duration of the disease was 8.5 ± 4.4 years among deceased patients. The length of the CAG repeats in the affected allele was 43.3 ± 3.5 repeats and the length was inversely correlated with the age at diagnosis (ß = -0.73, p < 0.001). The number of diagnoses varied regionally, whereas the repeat length did not. The frequency of the high risk HTT haplogroup A was 39% in Finnish chromosomes abstracted from the 1000 Genomes database compared to 53% in other European samples (p = 0.024). CONCLUSIONS: The annual rate of HD diagnoses and the age at diagnosis have increased. The prevalence of HD in the Finnish population is lower than that of other Caucasian populations, partly explained by the low frequency of HTT haplogroup A among the Finns.
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Enfermedad de Huntington/epidemiología , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Femenino , Finlandia/epidemiología , Humanos , Proteína Huntingtina , Enfermedad de Huntington/diagnóstico , Enfermedad de Huntington/genética , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Proteínas del Tejido Nervioso/genética , Prevalencia , Estudios Retrospectivos , Estadísticas no Paramétricas , Expansión de Repetición de Trinucleótido/genéticaRESUMEN
Here, we present a patient with Creutzfeldt-Jakob disease (CJD) who developed initial symptoms mimicking progressive supranuclear palsy (PSP). Before the development of typical CJD symptoms, functional imaging supported a diagnosis of PSP when [(123)I]-FP-CIT-SPECT showed a defect in striatal dopamine transporter binding, while [(18)F]-fluorodeoxyglucose PET showed cortical hypometabolism suggestive of Lewy body dementia. However, the postmortem neuropathological examination was indicative of CJD only, without tau protein or Lewy body findings. This case demonstrates that CJD should be taken into account in rapidly progressing atypical cases of parkinsonism, even when functional imaging supports a diagnosis of a movement disorder.
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Akinetic crisis or acute akinesia is a life-threatening complication of Parkinson's disease (PD) with unknown pathophysiological mechanisms. Clinically, it resembles the neuroleptic malignant syndrome, and dopaminergic drugs are transiently ineffective in the acute phase of the condition. There are no published dopaminergic functional imaging studies on PD patients with akinetic crisis. Here we report 2 advanced PD patients with akinetic crisis who were scanned with SPECT using brain dopamine transporter ligand [(123)I]FP-CIT. The first patient was additionally scanned before the condition developed, and the second patient was scanned after recovery. Striatal dopamine transporter binding was lower during than before the crisis, and both patients showed a nearly complete loss of dopamine transporter binding during the crisis. Serial imaging showed that the uptake remained negligible despite an improvement in motor function after recovery. Akinetic crisis in PD appears to be associated with a particularly severe loss of presynaptic striatal dopamine function that does not improve after recovery. Apart from presynaptic dopaminergic function, other dopaminergic or nondopaminergic mechanisms are involved in the clinical improvement of motor functions after akinetic crisis in PD.
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Natalizumab medication used in the treatment of active relapsing-remitting multiple sclerosis is associated with a risk of contracting progressive multifocal leukoencephalopathy (PML). Current risk of the PML disease in connection with natalizumab therapy in multiple sclerosis patients is 2.77/1,000. By December 2012, more than 108,000 multiple sclerosis patients worldwide have received natalizumab therapy. There are 350 multiple sclerosis patients receiving natalizumab in Finland. We describe the first one of the two Finnish multiple sclerosis patients having so far been diagnosed with PML disease as a complication of natalizumab therapy.
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Anticuerpos Monoclonales Humanizados/efectos adversos , Leucoencefalopatía Multifocal Progresiva/inducido químicamente , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Finlandia/epidemiología , Humanos , Leucoencefalopatía Multifocal Progresiva/epidemiología , Natalizumab , RiesgoAsunto(s)
Enfermedades de los Ganglios Basales/diagnóstico por imagen , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Tomografía Computarizada de Emisión de Fotón Único , Anciano , Enfermedades de los Ganglios Basales/patología , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Femenino , Humanos , Tropanos , Proteínas tau/metabolismoRESUMEN
Epilepsy is a common manifestation of mitochondrial disease associated with mutations of the mitochondrial polymerase γ (POLG). Prognosis of mitochondrial epilepsy is often poor and there are few reports of successful treatment of POLG-related epilepsy. We describe a 26-year-old woman who experienced severe headache during a three-day period, followed by symptoms of visual flashing, speech difficulty, and generalised seizures. EEG recording showed non-convulsive status epilepticus (left occipital area) and brain MRI revealed parieto-occipital T2-hyperintensities. Visual aura and aphasia persisted despite antiepileptic medication with phenytoin, oxcarbazepine, and levetiracetam. Mitochondrial disorder was clinically suspected and a homozygous c.2243G>C mutation (p.Trp748Ser) was discovered in the POLG1 gene. The patient was then set on a low glycaemic index treatment (LGIT) variant of the ketogenic diet, after which the headaches, aphasia, and visual aura progressively improved and disappeared. She returned home two weeks after onset of symptoms and has not had further seizures. She continues to receive levetiracetam monotherapy and LGIT. We conclude that, at least for this patient, the combination of three antiepileptic drugs and LGIT is effective and well tolerated as treatment for severe episodes of POLG-related mitochondrial epilepsy.
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Anticonvulsivantes/uso terapéutico , ADN Polimerasa Dirigida por ADN/genética , Dieta Cetogénica/métodos , Epilepsia/dietoterapia , Enfermedades Mitocondriales/genética , Piracetam/análogos & derivados , ADN Polimerasa gamma , Epilepsia/tratamiento farmacológico , Epilepsia/etiología , Femenino , Índice Glucémico , Humanos , Levetiracetam , Enfermedades Mitocondriales/complicaciones , Piracetam/uso terapéutico , Adulto JovenRESUMEN
Autosomal recessive proximal spinal muscular atrophy is caused by deletions in the survival of motor neuron (SMN1) gene, while autoimmune myasthenia gravis is an acquired disorder. An association between these two diseases has not been reported. Our patient with intermediate spinal muscular atrophy (SMA type II) did not need alimentary or respiratory aid until age 51 when he suddenly developed bulbar weakness and respiratory insufficiency. Seropositive myasthenia gravis was confirmed and the corresponding symptoms resolved on treatment.
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Miastenia Gravis/complicaciones , Atrofias Musculares Espinales de la Infancia/complicaciones , Atrofias Musculares Espinales de la Infancia/diagnóstico , Autoanticuerpos/sangre , Eliminación de Gen , Humanos , Masculino , Persona de Mediana Edad , Miastenia Gravis/inmunología , Receptores Colinérgicos/inmunología , Atrofias Musculares Espinales de la Infancia/genética , Proteína 1 para la Supervivencia de la Neurona Motora/genéticaAsunto(s)
Fiebre/etiología , Cefalea/etiología , Tiroiditis Subaguda/diagnóstico , Adulto , Antiinflamatorios/administración & dosificación , Diagnóstico Diferencial , Femenino , Fiebre/diagnóstico , Glucocorticoides/administración & dosificación , Cefalea/diagnóstico , Humanos , Hipertiroidismo/diagnóstico , Prednisona/administración & dosificación , Tiroiditis Subaguda/tratamiento farmacológicoRESUMEN
PURPOSE: Polymerase gamma (POLG) is the sole enzyme in the replication of mitochondrial DNA (mtDNA). Numerous mutations in the POLG1 gene have been detected recently in patients with various phenotypes including a classic infantile-onset Alpers-Huttenlocher syndrome (AHS). Here we studied the molecular etiology of juvenile-onset AHS manifesting with status epilepticus and liver disease in three teenagers. PATIENTS AND METHODS: We examined 14- and 17-year-old female siblings (patients 1 and 2) and an unrelated 15-year-old girl (patient 3) with juvenile-onset AHS, sequenced POLG1, and the entire mtDNA, examined mtDNA deletions by amplification of the full-length mtDNA with the long PCR method and used real-time PCR to quantify mtDNA in the tissue samples. RESULTS: The initial manifestations were migraine-like headache and epilepsy, and the terminal manifestations status epilepticus and hepatic failure. A homozygous W748S mutation in POLG1 was detected in the three patients. No deletions or pathogenic point mutations were found in mtDNA, but all three patients had mtDNA depletion. CONCLUSIONS: POLG mutations should be considered in cases of teenagers and young adults with a sudden onset of intractable seizures or status epilepticus, and acute liver failure. The W748S POLG1 mutation seems to lead to tissue-specific, partial mtDNA depletion in patients with juvenile-onset Alpers syndrome. Valproic acid should be avoided in the treatment of epileptic seizures in these patients.