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T Klockgether

Publications and source records attributed to T Klockgether.

At least 19 recordsLinked to original sources
PubMed2006

Scale for the assessment and rating of ataxia: development of a new clinical scale.

OBJECTIVE: To develop a reliable and valid clinical scale measuring the severity of ataxia. METHODS: The authors devised the Scale for the Assessment and Rating of Ataxia (SARA) and tested it in two trials of 167 and 119 patients with spinocerebellar ataxia. RESULTS: The mean time to administer SARA in patients was 14.2 +/- 7.5 minutes (range 5 to 40). Interrater reliability was high, with an intraclass coefficient (ICC) of 0.98. Test-retest reliability was high with an ICC of 0.90. Internal consistency was high as indicated by Cronbach's alpha of 0.94. Factorial analysis revealed that the rating results were determined by a single factor. SARA ratings showed a linear relation to global assessments using a visual analogue scale, suggesting linearity of the scale (p < 0.0001, r(2) = 0.98). SARA score increased with the disease stage (p < 0.001) and was closely correlated with the Barthel Index (r = -0.80, p < 0.001) and part IV (functional assessment) of the Unified Huntington's Disease Rating Scale (UHDRS-IV) (r = -0.89, p < 0.0001), whereas it had only a weak correlation with disease duration (r = 0.34, p < 0.0002). CONCLUSIONS: The Scale for the Assessment and Rating of Ataxia is a reliable and valid measure of ataxia, making it an appropriate primary outcome measure for clinical trials.

Adolescent↗
PubMed2006

Methionine metabolism and phenotypic variability in X-linked adrenoleukodystrophy.

A combined genotype of polymorphisms of methionine metabolism has been associated with CNS demyelination in methotrexate-treated patients. Within a sample of 86 patients with X-linked adrenoleukodystrophy, this genotype was overrepresented in a subgroup of 15 patients with adrenomyeloneuropathy (AMN) with CNS demyelination (adrenoleukomyeloneuropathy) in comparison to 49 AMN patients without CNS demyelination ("pure" AMN; p = 0.002), suggesting that methionine metabolism might contribute to the phenotypic variability in adrenoleukodystrophy.

Adolescent↗
PubMed2006

[Oral treatment of vitamin B12 deficiency in subacute combined degeneration].

Vitamin B12 deficiency due to malnutrition or malabsorption may lead to pernicious anemia and neurological disorders. Although randomized prospective studies have shown that pernicious anemia can be safely treated with oral vitamin B12 even in the absence of intrinsic factor, it is still common practice to treat patients with neurological symptoms with intramuscular cyancobalamin injections. We report the successful oral treatment of subacute combined degeneration of the spinal cord in a 24-year-old woman closely monitored clinically with MRI and plasma levels of vitamin B12, homocysteine, and methylmalonic acid. We suggest monitored oral substitution therapy as first-line therapy for neurological disorders related to vitamin B12 deficiency.

Administration, Oral↗
PubMed2006

Does high-field MR imaging have an influence on the classification of patients with clinically isolated syndromes according to current diagnostic mr imaging criteria for multiple sclerosis?

BACKGROUND AND PURPOSE: Current MR imaging criteria for multiple sclerosis (MS) do not specify the magnetic field strength. The aim of this study was to investigate whether different MR imaging field strengths, specifically high-field MR imaging, have an impact on the classification of patients with clinically isolated syndromes suggestive of MS, according to MR imaging and diagnostic criteria. METHODS: In a prospective intraindividual comparative study, we examined 40 patients with clinically isolated syndromes (CIS) consecutively with a 1.5 T and 3T MR imaging system, including axial sections of T2 turbo spin-echo, fluid-attenuated inversion recovery, and T1 spin-echo, before and after injection of gadolinium-diethylene-triaminepentaacetic acid. Constant resolution parameters were used for both field strengths. High-signal-intensity white matter lesions with a size of >3 mm were counted and categorized according to their anatomic location in infratentorial, callosal, juxtacortical, periventricular, and other white matter areas. Assessment of the fulfilled Barkhof MR imaging and McDonald diagnostic criteria was made separately for both field strengths in every patient. RESULTS: Eleven patients fulfilled more MR imaging criteria at 3T. Two of these patients fulfilled the criterion of dissemination in space (DIS) according to the first definition of McDonald criteria, which is based on imaging criteria alone. Another patient had DIS only at 3T, according to the second definition of the McDonald criteria including CSF parameters. CONCLUSION: MR field strength, specifically high-field MR imaging, has a substantial influence on the classification of patients with CIS according to imaging and a mild influence on the classification according diagnostic criteria for MS, leading to consequences for prognostic classification, imaging guidelines, and clinical trials.

Adolescent↗
PubMed2005

The European Multiple System Atrophy-Study Group (EMSA-SG).

Introduction. The European Multiple System Atrophy-Study Group (EMSA-SG) is an academic network comprising 23 centers across Europe and Israel that has constituted itself already in January 1999. This international forum of established experts under the guidance of the University Hospital of Innsbruck as coordinating center is supported by the 5th framework program of the European Union since March 2001 (QLK6-CT-2000-00661). Objectives. Primary goals of the network include (1) a central Registry for European multiple system atrophy (MSA) patients, (2) a decentralized DNA Bank, (3) the development and validation of the novel Unified MSA Rating Scale (UMSARS), (4) the conduction of a Natural History Study (NHS), and (5) the planning or implementation of interventional therapeutic trials. Methods. The EMSA-SG Registry is a computerized data bank localized at the coordinating centre in Innsbruck collecting diagnostic and therapeutic data of MSA patients. Blood samples of patients and controls are recruited into the DNA Bank. The UMSARS is a novel specific rating instrument that has been developed and validated by the EMSA-SG. The NHS comprises assessments of basic anthropometric data as well as a range of scales including the UMSARS, Unified Parkinson's Disease Rating Scale (UPDRS), measures of global disability, Red Flag list, MMSE (Mini Mental State Examination), quality of live measures, i.e. EuroQoL 5D (EQ-5D) and Medical Outcome Study Short Form (SF-36) as well as the Beck Depression Inventory (BDI). In a subgroup of patients dysautonomic features are recorded in detail using the Queen Square Cardiovascular Autonomic Function Test Battery, the Composite Autonomic Symptom Scale (COMPASS) and measurements of residual urinary volume. Most of these measures are repeated at 6-monthly follow up visits for a total study period of 24 months. Surrogate markers of the disease progression are identified by the EMSA-SG using magnetic resonance and diffusion weighted imaging (MRI and DWI, respectively). Results. 412 patients have been recruited into the Registry so far. Probable MSA-P was the most common diagnosis (49% of cases). 507 patients donated DNA for research. 131 patients have been recruited into the NHS. There was a rapid deterioration of the motor disorder (in particular akinesia) by 26.1% of the UMSARS II, and - to a lesser degree - of activities of daily living by 16.8% of the UMSARS I in relation to the respective baseline scores. Motor progression was associated with low motor or global disability as well as low akinesia or cerebellar subscores at baseline. Mental function did not deteriorate during this short follow up period. Conclusion. For the first time, prospective data concerning disease progression are available. Such data about the natural history and prognosis of MSA as well as surrogate markers of disease process allow planning and implementation of multi-centre phase II/III neuroprotective intervention trials within the next years more effectively. Indeed, a trial on growth hormone in MSA has just been completed, and another on minocycline will be completed by the end of this year.

Animals↗
PubMed2005

[(11)C]d-threo-methylphenidate PET in patients with Parkinson's disease and essential tremor.

Twenty Parkinson's disease (PD) patients, 6 patients with essential tremor and 10 healthy controls were studied with the dopamine transporter ligand [(11)C]d-threo-methylphenidate ([(11)C]dMP) and positron emission tomography (PET) to assess dopamine terminal loss in relation to disease duration and motor disability. Dopamine transporter availability was expressed as [(11)C]dMP binding potential (BP(dMP)) in percentage of the mean of healthy controls. In PD patients (age at onset 57.7 +/- 8.9 yrs; disease duration 5.2 +/- 3.3 yrs; UPDRS motor score 24.2 +/- 9.8; Hoehn & Yahr 2.1 +/- 0.8; mean +/- SD) BP(dMP) was reduced to 30% (range: 11-55%) in the putamen and 52% (range: 14-96%) in the caudate nucleus. BP(dMP) in the putamen closely correlated with the UPDRS motor score (r = -0.79, p < 0.001), and disease duration (r = -0.76, p < 0.001) but not with age at onset. The correlation with the UPDRS score depended on akinesia and rigidity, while the tremor scores were related neither to putamen nor caudate BP(dMP). Interestingly, when plotted over disease duration, PD patients with severe asymmetry of symptoms showed significantly lower BP(dMP) in the contralateral putamen (exponential fit: 34% at onset) than the other PD patients (41% at onset), indicating a different symptomatic threshold of these subgroups and an even closer correlation with the hypothetical "true" disease duration. The exponential fit across all patients indicated a mean symptomatic threshold of 37% contra- and 62% ipsilateral, corresponding with an observed mean BP(dMP) of 51% (average contra- and ipsilateral) in those patients with disease duration less than one year. No differences in BP(dMP) were observed between patients with essential tremor and healthy controls. [(11)C]dMP appears to be a useful and sensitive marker of dopaminergic dysfunction in PD and can be used to assess and monitor disease severity.

Aged↗
PubMed2005

Sensorineural hearing loss in patients with chronic progressive external ophthalmoplegia or Kearns-Sayre syndrome.

In the present study we assessed the prevalence and nature of hearing loss in patients with chronic progressive external ophthalmoplegia (CPEO) or Kearns-Sayre syndrome (KSS) due to single large-scale mitochondrial DNA (mtDNA) deletion or mtDNA tRNA (Leu (UUR)) A3243G point mutation (A3243G PM). 14 patients with mtDNA deletion and three patients with A3243G PM underwent audiological evaluation comprising pure-tone and speech audiometry as well as transient evoked otoacoustic emissions (OAE). Audiological evaluation revealed hearing impairment in 10/17 patients. Hearing loss was mild to moderate predominantly affecting high frequencies in five patients with subjective hearing problems (three patients with mtDNA deletions, two patients with A3243G PM). Subclinical hearing deficits restricted to high frequencies were seen in further five asymptomatic patients (four patients with mtDNA deletions, one patients with A3243G PM). Audiological findings suggested a cochlear origin of hearing loss in all subjects. Our results demonstrate that CPEO or KSS patients due to mtDNA deletion or A3243G PM are at high risk of developing sensorineural hearing deficits.

Adult↗
PubMed2005

Neuropsychological outcome after chemotherapy for primary CNS lymphoma: a prospective study.

BACKGROUND: Combined radio- and chemotherapy for primary CNS lymphoma (PCNSL) is associated with a considerable risk of long-term neurotoxicity. The impact of high-dose methotrexate (MTX)-based chemotherapy alone on cognition and quality of life (QOL) is controversial. OBJECTIVE: To assess the impact of the tumor itself and its treatment with high-dose MTX-based chemotherapy on long-term cognition and QOL in patients with PCNSL. METHODS: Prospective neuropsychological examinations and MRI were performed in patients with PCNSL who were in complete remission for more than 12 months after completion of chemotherapy. A QOL assessment was performed at long-term follow-up. RESULTS: Twenty-three patients were eligible. The median follow-up period was 44 months after diagnosis. In long-term follow-up, 22 (95%) of 23 patients showed either preserved or improved cognitive functions as compared with pretreatment and immediate posttreatment baseline assessment. One patient showed an isolated decline in psychomotor speed. Eleven (48%) of 23 patients displayed at least mild cognitive deficits at long-term follow-up not related to therapy. Nineteen (83%) of 23 patients reported a good QOL. MRI revealed confluent white matter abnormalities in eight patients that were not associated with cognitive decline. CONCLUSION: In patients with primary CNS lymphoma (PCNSL) treated with a methotrexate (MTX)-based chemotherapy, no gross cognitive decline has to be expected as a long-term treatment effect. MTX-induced white matter changes apparent on MRI are not inevitably associated with cognitive impairment. Nevertheless, a substantial fraction of patients with PCNSL retain cognitive deficits as a residual symptom of the tumor.

Adult↗
PubMed2005

Heparin-induced thrombocytopenia in neurologic patients treated with low-molecular-weight heparin.

The authors prospectively studied the risk for immune-mediated heparin-induced thrombocytopenia (HIT) in neurologic patients during administration of low-molecular-weight heparin (LMWH) vs unfractionated heparin (UFH). None of 111 neurologic patients receiving LMWH developed HIT, whereas HIT occurred in 2.5% of 200 patients treated with UFH (p = 0.17). The rate of heparin-induced antibodies in patients treated with LMWH was lower than in patients treated with UFH (1.8 vs 20.5%; p < 0.001).

Adult↗
PubMed2005

MTX-induced white matter changes are associated with polymorphisms of methionine metabolism.

Methotrexate (MTX) is a folate antagonist inhibiting nucleic acid and methionine synthesis. Methionine is necessary for CNS myelination. In 42 patients with primary CNS lymphoma (PCNSL) treated with a systemic and intraventricular high-dose MTX-based polychemotherapy, the presence of a risk haplotype defined by polymorphisms influencing methionine metabolism referred a relative risk for CNS white matter changes of 4.7 (p = 0.001). The authors conclude that methionine metabolism influences MTX neurotoxicity.

Aged↗
PubMed2005

[Ataxias. Diagnostic procedure and treatment].

Ataxia disorders (or ataxias) include both hereditary and nonhereditary diseases of the cerebellum and spinal cord, all of which are clinically characterized by progressive ataxia. A distinction is made between ataxia disorders and focal diseases of the cerebellum (tumor, abscess, infarction, hemorrhage, demyelinating disease). Ataxias are classified according to the molecular causes, being divided into hereditary ataxias, sporadic degenerative ataxias, and acquired ataxias. The diagnostic tests to be applied should be selected to suit the individual clinical situation in each case. When a patient experiences disease onset before the age of 25 years and the disease affects only one generation autosomal recessive ataxias must be considered. If one of the patient's parents had a similar disease spinocerebellar ataxia (SCA) with a dominant autosomal mode of inheritance is probable. Patients with sporadic disease starting in adulthood may have an acquired ataxia, such as alcoholic cerebellar degeneration (ACD) or paraneoplastic cerebellar degeneration (PCD), or a sporadic degenerative ataxia, such as multiple system atrophy (MSA) or sporadic adult-onset ataxia (SAOA). Therapies based on the underlying molecular pathogenesis are available for a number of ataxia disorders.

Ataxia↗
PubMed2005

Creatine has no beneficial effect on skeletal muscle energy metabolism in patients with single mitochondrial DNA deletions: a placebo-controlled, double-blind 31P-MRS crossover study.

The purpose of our randomized, double-blind, placebo-controlled crossover study in 15 patients with chronic progressive external ophthalmoplegia (CPEO) or Kearns-Sayre syndrome (KSS) because of single large-scale mitochondrial (mt) DNA deletions was to determine whether oral creatine (Cr) monohydrate can improve skeletal muscle energy metabolism in vivo. Each treatment phase with Cr in a dosage of 150 mg/kg body weight/day or placebo lasted 6 weeks. The effect of Cr was estimated by phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS), clinical and laboratory tests. (31)P-MRS analysis prior to treatment showed clear evidence of severe mitochondrial dysfunction. However, there were no relevant changes in (31)P-MRS parameters under Cr. In particular, phosphocreatine (PCr)/ATP at rest did not increase, and there was no facilitation of post-exercise PCr recovery. Clinical scores and laboratory tests did not alter significantly under Cr, which was tolerated without major side-effects in all patients. Cr supplementation did not improve skeletal muscle oxidative phosphorylation in our series of patients. However, one explanation for our negative findings may be the short study duration or the limited number of patients included.

Adult↗
PubMed2005

Common genetic variants of homocysteine metabolism in ischemic stroke: a case-control study.

Hyperhomocysteinemia is a risk factor for ischemic stroke. We investigated five functional polymorphisms involved in homocysteine metabolism in each 159 stroke patients and controls. The folate-sensitive polymorphism methylenetetrahydrofolate reductase (MTHFR) c. 677 C > T (A222V) referred a non-significant risk of ischemic stroke (odds ratio: 1.20) in all patients, and homozygosity for MTHFR c. 677 C > T was associated with an earlier onset of stroke selectively in patients younger than 60 years (38 +/- 3 years vs. 45 +/- 1 years; P = 0.043). This study suggests that the investigated polymorphisms are no major risk factors for stroke, although MTHFR c. 677 C > T could be a minor factor of vulnerability especially in young patients (TT genotype), which might be helpful for the clinical work-up of stroke cases and for preventive dietary strategies.

Adult↗
PubMed2005

Dopamine transporter SPECT in patients with mitochondrial disorders.

BACKGROUND: Mitochondrial disorders may affect basal ganglia function. In addition, decreased activity of complex I of the mitochondrial electron transport chain has been linked to the pathogenesis of dopaminergic cell loss in Parkinson's disease. Objective : To investigate the dopaminergic system in patients with known mitochondrial disorders and complex I deficiency. METHODS: Dopamine transporter density was studied in 10 female patients with mitochondrial complex I deficiency by (123)I-FP-CIT (N-beta-fluoropropyl-2beta-carbomethyl-3beta-(4-iodophenyl)-nortropane) SPECT. RESULTS: No differences in (123)I-FP-CIT striatal binding ratios were observed and no correlation of the degree of complex I deficiency and striatal binding ratios could be detected. CONCLUSIONS: These data argue against the possibility that mitochondrial complex I deficiency by itself is sufficient to elicit dopaminergic cell loss.

Adult↗
PubMed2004

L-carnitine and creatine in Friedreich's ataxia. A randomized, placebo-controlled crossover trial.

Impaired oxidative phosphorylation is a crucial factor in the pathogenesis of Friedreich's ataxia (FA). L-carnitine and creatine are natural compounds that can enhance cellular energy transduction. We performed a placebo-controlled triple-phase crossover trial of L-carnitine (3 g/d) and creatine (6.75 g/d) in 16 patients with genetically confirmed FA. Primary outcome measures were mitochondrial ATP production measured as phosphocreatine recovery by 31Phosphorus magnetic resonance spectroscopy, neurological deficits assessed by the international co-operative ataxia rating scale and cardiac hypertrophy in echocardiography. After 4 months on L-carnitine phosphocreatine recovery was improved compared to baseline (p<0.03, t-test) but comparison to placebo and creatine effects did not reach significance (p=0.06, F-test). Ataxia rating scale and echocardiographic parameters remained unchanged. Creatine had no effect in FA patients. L-carnitine is a promising substance for the treatment of FA patients, and larger trials are warranted.

Adenosine Triphosphate↗