RESUMO
Myotonic dystrophy type 1, also known as Steinert's disease, is an autosomal dominant disorder with multisystemic clinical features affecting the skeletal and cardiac muscles, the eyes, and the endocrine system. Thiamine (vitamin B1) is a cofactor of fundamental enzymes involved in the energetic cell metabolism; recent studies described its role in oxidative stress, protein processing, peroxisomal function, and gene expression. Thiamine deficiency is critical mainly in the central and peripheral nervous system, as well as in the muscular cells. Our aim was to investigate the potential therapeutical effects of long-term treatment with thiamine in myotonic dystrophy type 1 in an observational open-label pilot study. We described two patients with myotonic dystrophy type 1 treated with intramuscular thiamine 100 mg twice a week for 12 or 11 months. We evaluated the patients using the grading of muscle strength according to Medical Research Council (MRC), the Muscular Impairment Rating Scale (MIRS), and the Modified Barthel index. High-dose thiamine treatment was well tolerated and effective in improving the motor symptomatology, particularly the muscle strength evaluated with the MRC scale, and the patients' activities of daily living using the Modified Barthel Index. At the end of treatment, the MRC score was 5 in the proximal muscles and 2-4 in the distal muscles (the MRC score before the treatment was 3-4 and 1-3, respectively). The MIRS grade improved by 25% compared to baseline for both patients. In patient #1, the Modified Barthel Index improved by 44%, and in patient #2 by 29%. These findings suggest that clinical outcomes are improved by long-term thiamine treatment.
RESUMO
Thiamine (vitamin B1) is a cofactor of fundamental enzymes of cell energetic metabolism; its deficiency causes disorders affecting both the peripheral and central nervous system. Previous studies reported low thiamine levels in cerebrospinal fluid and pyruvate dehydrogenase dysfunction in Friedreich ataxia (FRDA). We investigated the effect of long-term treatment with thiamine in FRDA, evaluating changes in neurological symptoms, echocardiographic parameters, and plasma FXN mRNA levels. Thirty-four consecutive FRDA patients have been continuously treated with intramuscular thiamine 100 mg twice a week and have been assessed with the Scale for the Assessment and Rating of Ataxia (SARA) at baseline, after 1 month, and then every 3 months during treatment. Thiamine administration ranged from 80 to 930 days and was effective in improving total SARA scores from 26.6 ± 7.7 to 21.5 ± 6.2 (p < 0.02). Moreover, deep tendon reflexes reappeared in 57 % of patients with areflexia at baseline, and swallowing improved in 63 % of dysphagic patients. Clinical improvement was stable in all patients, who did not show worsening even after 2 years of treatment. In a subgroup of 13 patients who performed echocardiogram before and during treatment, interventricular septum thickness reduced significantly (p < 0.02). Frataxin mRNA blood levels were modestly increased in one-half of treated patients. We suppose that a focal thiamine deficiency may contribute to a selective neuronal damage in the areas involved in FRDA. Further studies are mandatory to evaluate thiamine role on FXN regulation, to exclude placebo effect, to verify our clinical results, and to confirm restorative and neuroprotective action of thiamine in FRDA.
Assuntos
Ataxia de Friedreich/tratamento farmacológico , Tiamina/uso terapêutico , Complexo Vitamínico B/uso terapêutico , Adulto , Análise de Variância , Ecocardiografia , Feminino , Ataxia de Friedreich/genética , Expressão Gênica/efeitos dos fármacos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Exame Neurológico , Fatores de Transcrição Box Pareados/genética , Fatores de Transcrição Box Pareados/metabolismo , RNA Mensageiro , Fatores de TempoRESUMO
Primary torsion dystonia is a movement disorder characterised by sustained or intermittent involuntary muscle contractions causing abnormal movements, postures or both. In this study, 3 brothers affected by inherited primary dystonia 16 (DYT16) began an oral therapy with high-dose thiamine from November to December 2015. After 3â months, an important improvement of the motor symptoms was observed. Our results support the hypothesis that pathogenesis of the symptoms might be related to a dysfunction in mitochondrial oxidative phosphorylation due to a focal impairment of thiamine-dependent processes. Our results support some authors' hypothesis that dystonia might have a mitochondrial aetiology.
Assuntos
Distúrbios Distônicos/tratamento farmacológico , Tiamina/uso terapêutico , Complexo Vitamínico B/uso terapêutico , Adulto , Humanos , Masculino , Irmãos , Resultado do TratamentoRESUMO
OBJECTIVES: To investigate the potential clinical, restorative, and neuroprotective effects of long-term treatment with thiamine in Parkinson disease (PD). DESIGN: Observational open-label pilot study. SETTING: Outpatient neurologic rehabilitation clinic. PATIENTS AND METHODS: Starting in June 2012, we have recruited 50 patients with PD (33 men and 17 women; mean age, 70.4 ± 12.9 years; mean disease duration, 7.3 ± 6.7 years). All the patients were assessed at baseline with the Unified Parkinson's Disease Rating Scale (UPDRS) and the Fatigue Severity Scale (FSS) and began treatment with 100 mg of thiamine administered intramuscularly twice a week, without any change to personal therapy. All the patients were re-evaluated after 1 month and then every 3 months during treatment. RESULTS: Thiamine treatment led to significant improvement of motor and nonmotor symptoms: mean UPDRS scores (parts I-IV) improved from 38.55 ± 15.24 to 18.16 ± 15.08 (p = 2.4 × 10(-14), t test for paired data) within 3 months and remained stable over time; motor UPDRS part III score improved from 22.01 ± 8.57 to 9.92 ± 8.66 (p = 3.1 × 10(-22)). Some patients with a milder phenotype had complete clinical recovery. FSS scores, in six patients who had fatigue, improved from 53.00 ± 8.17 to 23.60 ± 7.77 (p < 0.0001, t test for paired data). Follow-up duration ranged from 95 to 831 days (mean, 291.6 ± 207.2 days). CONCLUSIONS: Administration of parenteral high-dose thiamine was effective in reversing PD motor and nonmotor symptoms. The clinical improvement was stable over time in all the patients. From our clinical evidence, we hypothesize that a dysfunction of thiamine-dependent metabolic processes could cause selective neural damage in the centers typically affected by this disease and might be a fundamental molecular event provoking neurodegeneration. Thiamine could have both restorative and neuroprotective action in PD.
Assuntos
Doença de Parkinson/tratamento farmacológico , Tiamina/administração & dosagem , Complexo Vitamínico B/administração & dosagem , Idoso , Antiparkinsonianos/administração & dosagem , Gerenciamento Clínico , Relação Dose-Resposta a Droga , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVES: A previous study on fatigue and related disorders in inflammatory bowel disease, patients improved after therapy with high-dose thiamine. Chronic fatigue that accompanies inflammatory and autoimmune diseases could be the clinical manifestation of a mild thiamine deficiency, probably due to a dysfunction of intracellular transport or enzymatic abnormalities. Fatigue is a common symptom after stroke. Some studies show a severe functional effect of this symptom, as well as a high mortality rate. Necrotic cell death after cerebral ischemia triggers the activation of the immune system, followed by an inflammatory response. It is likely that fatigue related to stroke could benefit from high-dose thiamine. Consequently, the authors began treating poststroke patients with oral or parenteral high-dose thiamine. DESIGN: Case study. MATERIALS AND METHODS: Three patients with stroke who also experienced fatigue were recruited. Severity of the fatigue was assessed by using the Fatigue Severity Scale. Blood free thiamine and thiamine pyrophosphate levels were within the healthy reference range in all the patients. Oral or parenteral therapy with high-dose thiamine was started. RESULTS: The therapy led to an appreciable improvement of fatigue. CONCLUSION: This observation suggests that poststroke fatigue and related disorders could be the manifestation of mild thiamine deficiency due to a dysfunction of intracellular transport of thiamine or to structural enzymatic abnormalities.
Assuntos
Isquemia Encefálica/complicações , Fadiga/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Deficiência de Tiamina/tratamento farmacológico , Tiamina/uso terapêutico , Complexo Vitamínico B/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Fadiga/etiologia , Feminino , Humanos , Masculino , Acidente Vascular Cerebral/complicações , Deficiência de Tiamina/complicaçõesRESUMO
OBJECTIVES: In a previous study on fatigue and related disorders in inflammatory bowel disease (IBD), we observed that IBD patients improved after treatment with high-dose thiamine. We hypothesized that the chronic fatigue accompanying inflammatory and autoimmune diseases is the clinical manifestation of a mild thiamine deficiency that is probably due to a dysfunction of the intracellular transport or to enzymatic abnormalities. Hashimoto's thyroiditis is both a common automimmune disease and cause of hypothyroidism. Although levothyroxine, a thyroid hormone, is the treatment of choice for hypothyroidism, a significant number of patients on thyroid hormone replacement therapy report not feeling well despite having thyroid function tests within the healthy range. Based on our hypothesis, we started treating the fatigue in patients affected by Hashimoto's thyroiditis and taking a thyroid hormone with thiamine. This is a report of the outcomes of three cases in which the fatigue component reported by patients with Hashimoto's thyroiditis was treated with thiamine. DESIGN: Three patients on thyroid hormone replacement because of Hashimoto's thyroiditis were treated for the fatigue component of the disease from May to July 2011. Fatigue was measured using the Fatigue Severity Scale. Free thiamine in the serum and thiamine pyrophosphate in red cells were tested before and after the therapy. All three patients received oral (600 mg/day) or parenteral (100 mg/ml every four days) doses of thiamine. RESULTS: Treatment with thiamine led to partial or complete regression of the fatigue within a few hours or days. CONCLUSION: As the administration of thiamine led to a partial or complete regression of the fatigue and related disorders, it is reasonable to infer that the administration of large quantities of thiamine restores thiamine-dependent processes. The mild thiamine deficiency suggested by fatigue and related disorders may be due a dysfunction of the intracellular transport of thiamine or to enzymatic abnormalities most likely related to the autoimmune process of the disease.
Assuntos
Doença de Hashimoto/tratamento farmacológico , Tiamina/administração & dosagem , Adulto , Fadiga/sangue , Fadiga/tratamento farmacológico , Fadiga/etiologia , Feminino , Doença de Hashimoto/sangue , Doença de Hashimoto/complicações , Terapia de Reposição Hormonal , Humanos , Pessoa de Meia-Idade , Tiamina/sangue , Deficiência de Tiamina/sangue , Deficiência de Tiamina/tratamento farmacológico , Deficiência de Tiamina/etiologia , Hormônios Tireóideos/administração & dosagemRESUMO
Parkinson's disease (PD) is a systemic disease with motor and non-motor deficits. We recruited three patients with newly diagnosed PD. They were not under anti-Parkinson's therapy. Plasmatic thiamine was within healthy reference range. We performed the Unified Parkinson's Disease Rating Scale (UPDRS) and started a parenteral therapy with high doses of thiamine. The therapy led to a considerable improvement in the motor part of the UPDRS ranging from 31.3% to 77.3%. From this clinical observation, it is reasonable to infer that a focal, severe thiamine deficiency due to a dysfunction of thiamine metabolism could cause a selective neuronal damage in the centres that are typically hit in this disease. Injection of high doses of thiamine was effective in reversing the symptoms, suggesting that the abnormalities in thiamine-dependent processes could be overcome by diffusion-mediated transport at supranormal thiamine concentrations.
Assuntos
Doença de Parkinson/tratamento farmacológico , Tiamina/administração & dosagem , Complexo Vitamínico B/administração & dosagem , Idoso , Feminino , Humanos , Masculino , Resultado do TratamentoRESUMO
The majority of the patients with multiple sclerosis (MS) experience fatigue. Some observations indicate that fatigue and related manifestations concomitant with MS could be associated with an intracellular mild thiamine deficiency. We recruited 15 patients with MS who also experience fatigue and assessed the severity of the fatigue using the Fatigue Severity Scale. Although blood thiamine and thiamine pyrophosphate levels were within normal limit in all the patients, high-dose thiamine therapy administered orally or parenterally led to an appreciable improvement of the fatigue. The absence of apparent decrease in blood thiamine despite the presence of symptoms referable to a mild thiamine deficiency suggests that these patients may have a dysfunction of the mechanisms of intracellular transport or structural enzymatic abnormalities. The administration of large quantities of thiamine was effective in reversing the fatigue in MS, suggesting that the abnormalities in thiamine-dependent processes could be overcome by diffusion-mediated transport at supranormal thiamine concentrations.
Assuntos
Fadiga/tratamento farmacológico , Esclerose Múltipla/complicações , Tiamina/administração & dosagem , Complexo Vitamínico B/administração & dosagem , Adulto , Idoso , Esquema de Medicação , Fadiga/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Friedreich's ataxia (FRDA) is an autosomal recessive inherited disorder characterised by progressive gait and limb ataxia, dysarthria, areflexia, loss of position sense and a progressive motor weakness of central origin. Some observations indicate that all symptoms of FRDA ataxia could be the manifestation of a thiamine deficiency because of enzymatic abnormalities. Two patients with FRDA were under rehabilitative treatment from February 2012 to February 2013. The scale for assessment and rating of ataxia was performed. The patient began an intramuscular therapy with 100 mg of thiamine every 3-5 days. Injection of high-dose thiamine was effective in reversing the motor failure. From this clinical observation, it is reasonable to infer that a thiamine deficiency due to enzymatic abnormalities could cause a selective neuronal damage in the centres that are typically affected by this disease.
Assuntos
Ataxia de Friedreich/tratamento farmacológico , Deficiência de Tiamina/complicações , Tiamina/uso terapêutico , Complexo Vitamínico B/uso terapêutico , Adulto , Ataxia/tratamento farmacológico , Ataxia/enzimologia , Ataxia/etiologia , Feminino , Ataxia de Friedreich/enzimologia , Ataxia de Friedreich/etiologia , Humanos , Masculino , Tiamina/administração & dosagem , Complexo Vitamínico B/administração & dosagemRESUMO
Living with fibromyalgia means living with chronic pain, fatigue, sleep disorders and other associated key symptoms. To date, pharmacotherapy generally produces modest benefits. Some observations indicate that the large majority of symptoms of fibromyalgia could be the clinical manifestation of a mild thiamine deficiency due to a dysfunction of the active transport of thiamine from the blood to the mitochondria or to enzymatic abnormalities. Between June and July 2011, we recruited three female patients affected by fibromyalgia. We proceeded with the study of the patients' history, a physical examination, an evaluation of chronic widespread pain using the Visual Numeric Scale and an evaluation of the fatigue using the Fatigue Severity Scale were also performed. The levels of thiamine and thiamine pyrophosphate in the blood were determined. After the therapy with high doses of thiamine, in the patients, there was an appreciable improvement of the symptoms.
Assuntos
Fibromialgia/tratamento farmacológico , Tiamina/uso terapêutico , Complexo Vitamínico B/uso terapêutico , Adulto , Fadiga/tratamento farmacológico , Fadiga/etiologia , Feminino , Fibromialgia/complicações , Humanos , Pessoa de Meia-Idade , Medição da Dor , Tiamina/administração & dosagem , Resultado do Tratamento , Complexo Vitamínico B/administração & dosagemRESUMO
OBJECTIVES: To demonstrate that fatigue and other disorders related to ulcerative colitis and Crohn's disease are the manifestation of an intracellular mild thiamine deficiency and not due to malabsorbtion, augmented requirements, or nutritional factors, and that this dysfunction is curable with high doses of thiamine administered orally or parenterally. DESIGN: In this pilot study, we treated fatigue in eight patients with ulcerative colitis and four patients affected by Crohn's disease from January to April 2011. The patients were recruited through general practitioners' surveys and among personnel and affiliated personnel of the clinic Villa Immacolata. Fatigue was measured using the chronic fatigue syndrome scale, and the determination of thiamine and thiamine pyrophosphate levels in the blood was carried out through blood tests. The levels of thiamine and thiamine pyrophosphate in the blood were normal. All patients were assigned to receive high doses of thiamine orally. Depending upon the body weight of each patient, dosage ranged from 600 mg/day (60 kg) to 1,500 mg/day (90 kg). The chronic fatigue syndrome scale as well as thiamine and thiamine pyrophosphate levels in the blood were measured 20 days after the beginning of the therapy. RESULTS: Ten patients out of twelve showed complete regression of fatigue, while the remaining two patients showed nearly complete regression of fatigue compared to the chronic fatigue syndrome scale scores before therapy. CONCLUSIONS: The absence of blood thiamine deficiency and the efficacy of high-dose thiamine in our patients suggest that fatigue is the manifestation of a thiamine deficiency, likely due to a dysfunction of the active transport of thiamine inside the cells, or due to structural enzymatic abnormalities. The administration of large quantities of thiamine increases the concentration in the blood to levels in which the passive transport restores the normal glucose metabolism in all cells and leads to a complete regression of fatigue.
Assuntos
Fadiga/tratamento farmacológico , Fadiga/etiologia , Doenças Inflamatórias Intestinais/complicações , Deficiência de Tiamina/tratamento farmacológico , Deficiência de Tiamina/etiologia , Tiamina/uso terapêutico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Tiamina/administração & dosagem , Resultado do TratamentoRESUMO
Spinocerebellar ataxia type 2 is a genetic disorder characterised by the degeneration of the cerebellum, its connections and degeneration in brainstem areas. Some observations indicate that high doses of thiamine may lead to the partial regression of the symptoms. One patient was under rehabilitative treatment from June 2011 to July 2012. We assessed the level of fatigue using the Fatigue Severity Scale. We performed the Scale for Assessment and Rating of Ataxia and Robertson Profile for Dysarthria (Italian version). Thiamine and thiamine pyrophosphate levels in the blood were within the healthy reference range. We started a parenteral therapy with 100 mg intramuscular every 7 days. The therapy led to a partial regression of fatigue within a few days. After about 3 months, a discreet improvement of motor symptoms especially in speech was observed. The symptoms could derive from a focal thiamine deficiency that could determine a selective neuronal loss.