High-dose olanzapine in Huntington's disease.

The few reports available on olanzapine in Huntington's disease (HD) are insufficiently documented and/or insufficiently dosed. We describe a 30-year-old woman with genetically confirmed HD who presented with severe chorea. She was not able to eat or dress without help and did not respond to haloperidol; the motor scale of the Unified HD Rating Scale (UHDRS-I) revealed 65 of a possible 124 points. After admission, we treated the patient with a high dose of olanzapine (30 mg daily). The chorea almost ceased in the next 2 days, she was able to eat and walk without assistance (UHDRS-I of 21 points), and fine motor tasks improved, as well as gait and eye movements. This effect lasted for 5 months. We conclude that high-dose olanzapine appears to be useful in grave choreatic attacks.

[Adrenoleukodystrophy mimicking multiple sclerosis]. / Adrenoleukodystrophie kann Multiple Sklerose imitieren.

The article describes the development of symptoms in a 40-year-old female patient who is a symptomatic carrier of X-linked adrenoleucodystrophy (ALD). ALD is characterized by impaired peroxisomal beta-oxidation of very long chain fatty acids and is associated with mutations of the ALD gene, resulting in a defective peroxisomal membrane-transport protein. Our patient's symptoms are identical to those found in multiple sclerosis, showing spastic paraparesis of the lower limbs with marked sensory deficits, visual disturbances in the right eye, and bladder difficulties. Visual and auditory evoked potentials were pathological, and a cranial MRI revealed multiple periventrical white-matter lesions. We found increased intrathecal immunoglobulin production. Diagnosis was established by high concentrations of very long chain fatty acids in serum and in dermal fibroblasts after the same was found in our patient's son. In familial multiple sclerosis, ALD should be excluded in male and female patients.

Compactotomy in Huntington's chorea.

Advances in neuroradiological and neurosurgical techniques have lead to a growing interest in functional neurosurgical interventions for medically intractable movement disorders. The majority of these procedures are performed in patients with hypokinetic movement disorders, especially Parkinson's disease. However, relatively few interventions were done in hyperkinetic disorders such as Huntington's disease (HD), mainly owing to the lack of an adequate target nucleus. We have recently described the case of a reversible chorea in a genetically confirmed HD patient. We subsequently identified a marked bilateral degeneration of the substantia nigra as the probable reason for choreatic cessation. We therefore suggest that primary striatal atrophy causing hyperkinesia and secondary substantia nigra atrophy favouring hypokinesia were balanced in this patient, thus resulting in a close-to-physiologic GABAergic basal ganglia output. We postulate that deep brain stimulation of the substantia nigra pars compacta may ameliorate hyperkinesia in choreatic movement disorders, thus representing the first effective therapy in Huntington's chorea. Several lines of evidence in recent neurophysiological research support our hypothesis and are discussed below.

Autonomic nervous function assessment using thermal reactivity of microcirculation.

There are only a few reliable objective methods of diagnosing peripheral neuronal damage suitable for routine use; the most important is based on measurement of nerve conduction velocity, which only shows changes when severe disturbances are already present. However, it is precisely at this stage that the possibilities of therapy are no longer satisfactory. As small fibres are affected earlier in the course of most forms of PNP than the large ones, assessment of afferent as well as efferent C-fibre function gains importance in the management of this widespread disease. In assessment of autonomic dysfunction, variability of the heartbeat with deep breathing or the Valsalva manoeuvre is a good and generally accepted test, although not strongly associated with other PNP test abnormalities. However, axonal degeneration starts in the most distal parts of the axon due to impaired axonal transport. Therefore, the longest C-fibres, i.e. in the lower extremities, are affected first, and incipient changes are most prominent there. For this reason HLDF, a reflex response of the skin blood flow stimulated by heat, has advantages in assessment of early C-fibre dysfunction. Considering the fact that the afferent and efferent sympathetic C-fibres are involved in regulation of microcirculation, the skin blood flow regulation is investigated by means of laser Doppler flowmetry. The microcirculation is stimulated by heat and the reaction of microcirculation is assessed as a value for the function of afferent and efferent (sympathetic) C-fibres. The results of this method are in close correlation with electrophysiologic tests, which is not achieved with sudomotor function.

[Speech disturbances and dyskinesias as initial symptoms of cortico- basal degeneration]. / Sprachstörungen und Dyskinesien als Initialsymptome einer kortikobasalen Degeneration.

The article describes the development of symptoms in a 59-year-old patient. Dyskinesia and speech disorder were the only clinical features in the beginning. Increased immunological parameters and only slight hypokinetic-rigid signs for a long time made the diagnostical and therapeutical process more difficult, as well as atypical findings in neuroimaging techniques. Corticobasal degeneration was diagnosed about 6 years after onset of clinical symptoms.

Lipoprotein(a) serum concentration and apolipoprotein(a) phenotype correlate with severity and presence of ischemic cerebrovascular disease.

BACKGROUND AND PURPOSE: Serum lipoprotein(a) [Lp(a)] levels are genetically determined and considered to be an independent risk factor for atherosclerosis. The aim of this study was to provide a complete analysis of Lp(a) serum levels, apolipoprotein(a) phenotypes, and other lipid parameters for different forms of severity of symptomatic ischemic cerebrovascular disorders as well as for different stages of carotid atherosclerosis. METHODS: Lp(a) concentration, apolipoprotein(a) phenotype, triglyceride, low-density lipoprotein, high-density lipoprotein, and total cholesterol levels of blind-coded specimens as well as degree of carotid artery stenosis were assessed in a consecutive series of patients with ischemic cerebrovascular disease. We evaluated 265 male (34%) and female (66%) patients (mean age, 51 +/- 7.4 years) with transient ischemic attack (55.8%), prolonged reversible ischemic neurological deficits (28.3%), and cerebral infarction (15.9%) as well as 288 male (30%) and female (70%) control subjects (mean age, 51 +/- 7.1 years). All subjects were white. RESULTS: Lp(a), total, and low-density lipoprotein cholesterol were statistically significantly elevated in all patients compared with control subjects. Lp(a) correlated with the severity of symptomatic cerebrovascular disease and the degree of carotid stenosis. Logistic regression analysis revealed Lp(a) as the best single marker for the presence of cerebrovascular disease (P < .001) followed by high-density lipoprotein cholesterol (P = .003) and triglycerides (P = .049). With a cutoff of 20 mg/dL of Lp(a), the odds ratio for a subject to have had ischemic stroke with elevated Lp(a) was 20.3 and 23.7 depending on the method of the Lp(a) estimation, whereas the odds ratio when the sonography score was > 0 was 15.4. The investigation of the distribution of the apo(a) phenotypes revealed that 16.73% of the control subjects had major isoforms < or = 580 kD molecular weight (B, F, S1, S2) versus 42.65% of the patients' group (P < .001). These isoforms were also present in 14.71% of all individuals with a sonography score of 0 but in 52.30% of all individuals with a sonography score > 0 (P < .001). CONCLUSIONS: This case-control study shows that an elevated Lp(a) level is the primary factor associated with the presence of ischemic cerebrovascular disease and that the increased portion of the smaller-molecular-weight apo(a) isoforms in patients and individuals with a sonography score > 0 points toward an inherited predisposition for this disease.

Evaluation of the Cobas Core system for use in routine diagnosis of thyroid disorders.

The aim of this clinical study was to evaluate the TSH, FT4, FT3, T3, and T4 assays designed for use on the Cobas Core Immunoassay Analyzer. Performance of these enzyme immunoassays (EIAs) was compared with well established and routinely used radioimmunoassays (RIA) or immunoradiometric assay (IRMA). In the first part of the study, the between-run and within-run data as well as the linearity of the Cobas Core assays was carried out, showing a very high precision; most coefficients of variation (CVs) were below 8%. In the second part of the study, serum samples from patients with different thyroid diseases were evaluated, and the results compared with those obtained by RIA or by IRMA. All results were highly comparable with the clinical aspects of all investigated thyroid disorders, and the data of TSH, FT4, T3 and T4 were completely in concordance with those assessed by RIA or IRMA methods; however, only the FT3 assays had a moderately correlation. In contrast to RIA methods, Cobas Core EIAs provided precise results in patients with thyroid hormone transport protein anomalies or T4/T3 autoantibodies; moreover, elevated serum concentrations of thyroxine binding globulin (TBG) did not affect measurement of total thyroid hormone concentrations.

[Late potentials in high resolution ECG in thyroid gland dysfunction]. / Spätpotentiale im High-Resolution-EKG bei Schilddrüsen-Funktionsstörungen.

In this study we examined 278 patients as to the effect of thyroidal dysfunctions upon late-potential parameters in high-resolution ECG (HR-ECG). It could be demonstrated that both hyper- and hypothyroidism tend to produce late potentials. It is remarkable that even "subclinical" dysfunctions reveal significant alterations in HR-ECG. As late potentials represent a risk factor for ventricular arrhythmias these results are an additional indication that already "subclinical" dysfunctions of thyroid gland call for an appropriate therapy. In hyperthyroidism late potentials may be eliminated rapidly by propranolol even in low dosages.

Familial dysalbuminaemic hyperthyroxinaemia and inherited partial TBG deficiency: first report.

BACKGROUND: Abnormalities of the serum thyroid hormone binding proteins are not uncommon but, when properly assessed, they do not present diagnostic difficulties. In contrast, the presence of two inherited defects of thyroid hormone transport, of the type presented in the family described here, may cause a major problem in diagnosis and has not been described previously. METHODS: All conventional thyroid function tests were carried out. In addition, thyroid hormone binding to serum proteins was assessed by agarose gel electrophoresis, and thyroxine binding globulin by immunoassays and by immunodiffusion. The affinity of TBG for thyroxine and its maximal binding capacity were assessed by Scatchard analysis. RESULTS: Tests carried out on 22 members of the family revealed familial dysalbuminaemic hyperthyroxinaemia in 10 family subjects. All five living siblings of the propositus had familial dysalbuminaemic hyperthyroxinaemia and two tested transmitted this trait to their children and grandchildren. This was not the case with the propositus. Partial thyroxine binding globulin deficiency only, inherited presumably from the propositus' mother, was found in two family members. Both thyroxine binding globulin deficiency and familial dysalbuminaemic hyperthyroxinaemia were detected in the propositus and in his male nephew, masking the typical laboratory abnormalities associated with each of these defects. CONCLUSIONS: Coexistence of two inherited defects of thyroid hormone transport proteins produce atypical thyroid function test abnormalities, which can be misinterpreted as thyroid hormone dysfunction.

[Familial dysalbuminemic hyperthyroxinemia in long-term amiodarone treated patients]. / Familiäres dysalbuminämisches Hyperthyroxinämie-syndrom unter Amiodaron-Langzeitbehandlung.

A serum sample of an outpatient, under long-term amiodarone (AM) treatment was submitted for routine checkup of thyroid function parameters. It revealed the pattern of euthyroid dysalbuminemic hyperthyroxinemia. Since no results have been published so far covering the influence of amiodarone on the specific thyroxine binding proteins, we undertook a prospective study to investigate 28 amiodarone patients, comparing these with a series of age and sex matched euthyroid subjects. Not one amiodarone patient showed changed radio-T4 distribution against the normal group. Yet, in 3 relatives of the propositus, familial screening revealed the typical pattern of thyroid function tests and of T4 distribution in radio immune ice gel electrophoresis, respectively, proving familial dysalbuminemic hyperthyroxinemia syndrome. Thus, it is most likely that this syndrome has been prevalent already prior to the amiodarone administration and consequently amiodarone was of no influence on thyroxine transport protein patterns.

Cerebrovascular disease and Lp(a): its role in atherosclerotic plaque formation and vessel wall elasticity of the carotid arteries.

Lp(a) was found to represent an independent risk factor of extracranial carotid atherosclerosis (CA). Here we report on an investigation with 808 subjects randomly selected from stroke patients as well as from asymptomatic subjects. Serum levels of Lp(a), total cholesterol (TC), HDL-C and the ratios of TC/HDL-C and LDL-C/HDL-C correlated highly significantly with the carotid score using a univariate test. Performing a discriminant analysis, the following ranking was obtained: Lp(a), HDL-C, LDL-C/HDL-C. Evaluation of the vessel wall elasticity in 746 subjects revealed Lp(a) to be the only highly significant parameter. Thus, Lp(a) has to be taken into consideration when establishing a risk profile of CA.