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1.
We report here the results of 24 months' treatment with oral miglustat of a patient with mild-to-moderate Gaucher's disease (GD) and Parkinsonism. The patient's progressive Parkinsonian tremor, in addition to restricted vascular access, necessitated switching treatment for GD from intravenously infused enzyme replacement therapy (ERT) that had been administered for the previous 7 years. With control of haematological parameters and markers of GD activity improved or maintained and no notable adverse effects, miglustat treatment proved an effective and well-tolerated therapeutic alternative to ERT. Oral miglustat should be considered for the treatment of patients with type I GD and concurrent movement disorders who are unsuitable for ERT.  相似文献   

2.
IntroductionGaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by a deficiency of acid β-glucosidase encoded by the GBA gene. In patients with GD, childhood onset parkinsonian features have been rarely described.MethodsTwin siblings with GD are described, including clinical follow-up and treatment response. Bone marrow, enzyme activity studies and genotyping were performed.ResultsBy age 9 months, symptoms at onset were thrombocytopenia and splenomegaly. By age 2, hypokinesia, bradykinesia and oculomotor apraxia were observed. By age 5 a complete rigid hypokinetic syndrome was stablished in both patients, including bradykinesia, tremor and rigidity. Treatment with imiglucerase, miglustat, ambroxol and levodopa were performed. Levodopa showed a good response with improvement in motor and non-motor skills. Foamy cells were found in the bone marrow study. Glucocerebrosidase activity was 28% and 26%. Sanger sequencing analysis identified a missense mutation and a complex allele (NP_000148: p.[(Asp448His)]; [(Leu422Profs*4)]) in compound heterozygosity in GBA gene.ConclusionsTwo siblings with neuronopathic GD with an intermediate form between type 2 and 3, with a systemic and neurological phenotype are described. The complex neurological picture included a hypokinetic-rigid and tremor syndrome that improved with levodopa treatment. These conditions together have not been previously described in pediatric GD. We suggest that in children with parkinsonian features, lysosomal storage disorders must be considered, and a levodopa trial must be performed. Moreover, this report give support to the finding that GBA and parkinsonian features share biological pathways and highlight the importance of lysosomal mechanisms in parkinsonism pathogenesis, what might have therapeutic implications.  相似文献   

3.
PURPOSE: To describe the clinical features of a large kindred with familial infantile myoclonic epilepsy (FIME) with autosomal recessive inheritance, and to discuss the nosology of the early infantile myoclonic epilepsies (IMEs). METHODS: The family descends from the intermarriage of two couples of siblings. In a previous study, we mapped the genetic locus to chromosome 16p13.We analyzed results of family records and personal history, psychomotor development, neurologic examination, epilepsy features, and EEG recordings for each subject. RESULTS: FIME has a strong penetrance (eight affected of 14 subjects) and a homogeneous clinical picture. Like the benign form of infantile myoclonic epilepsy (BIME), FIME is a true idiopathic IME with unremarkable history, no neurologic or mental impairment, good response to treatment, and normal interictal EEG pattern. Conversely, onset with generalized epileptic seizures without fever (four patients) or with fever (one patient), frequency and duration of the myoclonic seizures, occurrence of generalized tonic--clonic seizures (GTCSs) in all patients and persistence of seizures into adulthood are characteristics of the severe infantile myoclonic epilepsy (SIME). CONCLUSIONS: Clinical overlap probably exists among the myoclonic epilepsies of infancy. FIME differs from other forms of IME in its phenotypic features. The peculiar mode of inheritance is explained by the genetic background of the family. Genetic studies suggest linkage to chromosome 16 in familial cases of true IME.  相似文献   

4.
Clinical experience in open-label studies and anectodal reports suggest that levetiracetam is effective in generalized epilepsy. In this open-label prospective study, 19 patients (3 men, 16 women) affected by idiopathic generalized epilepsy were followed for at least 6 months following the introduction of levetiracetam. Patients were categorized according to syndrome subtype: juvenile myoclonic epilepsy (8), juvenile absence epilepsy (5), childhood absence epilepsy (4), and eyelid myoclonia with absences (2). Eleven patients received levetiracetam as monotherapy, eight as add-on therapy. Effectiveness was demonstrated in 18 patients: 13 became seizure-free (five juvenile myoclonic epilepsy, five juvenile absence epilepsy, three childhood absence epilepsy), and five achieved significant reductions in seizure frequency (three juvenile myoclonic epilepsy, one childhood absence epilepsy, one eyelid myoclonia with absences). Only one patient experienced no change in seizure frequency (eyelid myoclonia with absences). Clinical improvement was accompanied by EEG abnormality suppression or reduction. Levetiracetam was well tolerated; no patient reported side-effects.  相似文献   

5.
Topiramate in patients with juvenile myoclonic epilepsy   总被引:3,自引:0,他引:3  
BACKGROUND: Topiramate is a broad-spectrum agent effective against primarily generalized tonic-clonic seizures (PGTCS) as well as partial-onset seizures. Juvenile myoclonic epilepsy is one of the most common idiopathic generalized epilepsies, with most patients experiencing PGTCS. OBJECTIVE: To evaluate topiramate as add-on therapy in patients with juvenile myoclonic epilepsy. DESIGN: Post-hoc analysis of a patient subset from 2 multicenter, double-blind, randomized, placebo-controlled, parallel-group trials. SETTING: Eighteen centers in the United States; 10 centers in Europe; 1 center in Costa Rica (primary trials). PATIENTS: A total of 22 patients with juvenile myoclonic epilepsy participating in placebo-controlled trials assessing topiramate (target dose, 400 mg/d in adults) in inadequately controlled PGTCS. MAIN OUTCOME MEASURE: Reduction of PGTCS. RESULTS: A 50% or more reduction of PGTCS in 8 of 11 topiramate-treated patients (73%) and 2 of 11 placebo-treated patients (18%) (P = .03). Reductions in myoclonic, absence, and total generalized seizures were also observed, although topiramate vs placebo differences did not achieve statistical significance. CONCLUSION: As a broad-spectrum agent, topiramate is an effective option for patients with juvenile myoclonic epilepsy.  相似文献   

6.
We report a patient with Gaucher's disease (GD) developing prominent neurological abnormalities in adult life confirming the existence of an adult neuronopathic form of GD. In this adult-onset form, an akinetic-rigid syndrome poorly responsive to dopatherapy, supranuclear gaze palsy, myoclonic jerks, seizures, cerebellar ataxia, cognitive and psychotic disturbances are frequent manifestations.The widely used clinical classification seems inadequate since it does not consider this rare form of GD.Until further understanding of the pathogenesis of the disease is achieved it is not possible to predict accurately which patients will or will not have late-onset nervous system involvement.  相似文献   

7.

Objective

To describe the clinical presentation of 10 patients with type 3 Gaucher disease and the clinical evolution of nine of them following specific therapy regimes. Methods: The follow-up of these 10 patients was between 2 and 15 years. The clinical history was provided by each patient’s general practitioner and a final clinical evaluation was made by two different physicians including a neurologist. One patient received no treatment, eight received enzyme replacement therapy (ERT) and one received ERT combined with substrate reduction therapy (SRT, miglustat). Results: The clinical presentations were heterogeneous and most phenotypes reported for type 3 Gaucher disease were represented. The neurological involvement stabilized or improved in six patients under ERT with a follow-up of 2-15 years. Four of them showed isolated oculomotor signs only that improved or remained unchanged during the follow-up. Of two patients with progressive myoclonic epilepsy, the outcome was clearly unfavorable in one receiving ERT and disputable for the other receiving ERT + SRT. An unfavorable neurological outcome was observed in another patient in whom the ERT dose had been reduced before clinical decline. Conclusion: The stabilization of the clinical course in most patients is noteworthy. Though further evidence is needed from a larger series in order to draw any definite conclusions, our data suggest that ERT may be effective in preventing the evolution of neurological disturbances associated with type 3 Gaucher disease in some patients. However, the clinical course of the two patients with progressive myoclonic epilepsy was not influenced by ERT, as previously reported. In accordance with that reported in the literature, data from our series suggest that the outcome of patients undergoing ERT depends on the type of clinical involvement, treatment onset and dose. Genotype may also be an important factor, with p.L444P/p.L444P possibly indicating a better outcome.  相似文献   

8.

Objective

To evaluate the efficacy and safety of miglustat, concomitant with enzyme replacement therapy (ERT), in patients with Gaucher's disease type 3 (GD3).

Methods

This 24‐month, phase II, open‐label clinical trial of miglustat in GD3 was conducted in two phases. During the initial 12 months, patients were randomized 2:1 to receive miglustat or “no miglustat treatment.” The randomized phase was followed by an optional 12‐month extension phase in which all patients received miglustat. All patients received ERT during the 24‐month period. The primary efficacy end points were change from baseline to months 12 and 24 in vertical saccadic eye movement velocity as determined by the peak amplitude versus amplitude regression line slope. Secondary end points included changes in neurological and neuropsychological assessments, pulmonary function tests, liver and spleen organ volumes, hematological and clinical laboratory assessments, and safety evaluations.

Results

Thirty patients were enrolled, of whom 21 were randomized to miglustat and 9 to “no miglustat treatment.” Twenty‐eight patients entered the 12‐month extension phase. No significant between‐group differences in vertical saccadic eye movement velocity or in the other neurological or neuropsychological evaluations were observed. Organ volumes and hematological parameters remained stable in both treatment groups, but improvement in pulmonary function and decrease of chitotriosidase levels were observed with miglustat compared with patients receiving ERT alone.

Interpretation

Miglustat does not appear to have significant benefits on the neurological manifestations of GD3. However, miglustat may have positive effects on systemic disease (pulmonary function and chitotriosidase activity) in addition to ERT in patients with GD3. Ann Neurol 2008;64:514–522  相似文献   

9.
The authors present 11 cases of idiopathic generalized epilepsy that began in adulthood at a mean age of 39 years. All patients had myoclonic jerks, five had absence seizures, and nine had infrequent generalized tonic-clonic seizures. A majority had a family history of seizures. EEG in all patients showed generalized epileptiform abnormalities, whereas neuroimaging and neurologic examination results were normal. This series appears to represent a previously undescribed idiopathic generalized epilepsy syndrome of adult myoclonic epilepsy.  相似文献   

10.
Zonisamide, a newer antiepileptic drug (AED) with multiple mechanisms of action, has been increasingly used in patients with generalized epilepsies. This case study focuses on the effects of zonisamide on the EEG of a patient with juvenile myoclonic epilepsy. The patient had complete resolution of myoclonic jerks and absence and generalized seizures on introduction and titration of therapy with zonisamide; his EEG showed almost complete resolution of generalized spike and wave discharges and electrographic absence seizures. This case report suggests that zonisamide may be effective in the treatment of medication-resistant idiopathic generalized epilepsy and that it may lead to a significant improvement of the EEG.  相似文献   

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