Impaired heart rate variability in cervical dystonia is associated to depression.

Causes of cardiovascular autonomic dysfunction in cervical dystonia (CD) are poorly understood. Studies examining effects of botulinum neurotoxin (BoNT) therapy on heart rate variability (HRV) yielded contradictory results. There is compelling evidence that depression shifts autonomic balance towards sympathetic predominance. As depression is the most frequent non-motor symptom in CD, we sought to determine if it is associated to dysfunction of cardiovascular autonomic regulation. Standardized interviews, clinical examinations, self-rating forms, autonomic symptom questionnaire, and automated autonomic testing in outpatients with idiopathic CD were used. Cardiovascular autonomic screening encompassed five different analyses of HRV, and testing of orthostasis. 85 CD patients participated in the study. 21% of them had HRV impairment, 14% orthostatic hypotension. 30% of CD patients had symptoms of depression. In those, decreased HRV was more frequent than in CD patients without mood disturbance (40 vs. 13%; p = 0.008). CD patients with and without depression had no other significant differences, including demographics, dystonia severity, comorbidity, medication, or BoNT therapy. Cardiovascular autonomic imbalance with sympathetic predominance is a non-motor manifestation of CD, associated to depression. Impaired HRV is a cardiovascular risk factor, moreover, emphasizing the need to identify and treat depression in dystonia.

Features of probable multiple system atrophy patients identified among 4770 patients with parkinsonism enrolled in the multicentre registry of the German Competence Network on Parkinson's disease.

We identified 221 patients with probable multiple system atrophy (MSA) among 4770 patients enrolled in the multicentre registry of the German Competence Network on Parkinson's disease (PD) according to the established consensus criteria to characterize their clinical presentation. Analyses of more than 100 recorded clinical items revealed several specifics: I) 50% of patients with probable MSA had asymmetry of symptoms at disease onset and tremor at rest was present in 25%; II) a positive response to levodopa was recorded in 51% of patients identified initially with severe autonomic failure and cerebellar ataxia; III) a positive family history was recorded in 11% (n = 23), two of these patients were identified with spinocerebellar ataxia type 3 (SCA3). Thus asymmetry of symptoms, tremor at rest and a positive response to levodopa are not as specific for idiopathic PD as believed previously. Patients with SCA3 may present with the clinical features of MSA.

Sporadic adult onset ataxia of unknown etiology : a clinical, electrophysiological and imaging study.

BACKGROUND: The sporadic adult onset ataxias of unknown etiology (SAOA) denote the non-hereditary degenerative adult onset ataxias that are distinct from multiple system atrophy (MSA). OBJECTIVE: To define and characterize the clinical phenotype of sporadic adult onset ataxia of unknown etiology (SAOA). DESIGN: A survey of clinical features, nerve conduction and evoked potentials, autonomic tests, and magnetic resonance imaging (MRI)-based brain morphometry was conducted in patients with SAOA. PATIENTS: Study subjects were a consecutive sample of 27 patients (11 male, 16 female) who met the diagnostic criteria for SAOA (age 55 +/- 13 years; age at disease onset 47 +/- 14 years; disease duration 8 +/- 7 years). RESULTS: All patients presented with a cerebellar syndrome. The most frequent extracerebellar symptoms were decreased vibration sense in 70% and decreased or absent ankle reflexes in 33% of the patients. Nerve conduction studies revealed a polyneuropathy in 26% of the patients. Somatosensory evoked potentials were abnormal in 44%, and central motor conduction time in 17% of patients. Autonomic testing revealed an affected autonomic nervous system in 58% of patients. Voxel-based brain morphometry showed a predominant reduction of gray matter in the cerebellum which was significantly correlated with disease stages. A loss of white matter was found in both middle cerebellar peduncles and the outer edge of the pons. CONCLUSIONS: The data show that SAOA is a predominantly, but not exclusively cerebellar disorder. Clinical, electrophysiological, and imaging findings showed some similarities with multiple system atrophy which raises the question of an overlap of these two disorders.

Saccade velocity as a surrogate disease marker in spinocerebellar ataxia type 2.

We measured in 82 spinocerebellar ataxia type 2 (SCA2) patients and in 80 controls maximal saccade velocity (MSV) and correlated it to polyglutamine expansion size and disease duration. MSV is strongly decreased in SCA2 patients and is influenced mostly by polyglutamine size.

Cerebellar ataxia with glutamic acid decarboxylase autoantibodies.

Degenerative cerebellar ataxia with autoantibodies against glutamic acid decarboxylase (GAD) is a rare disorder and may represent a subset of ataxias previously classified as idiopathic. The authors report a patient with progressive cerebellar ataxia, insulin-dependent diabetes mellitus, and GAD antibodies who responded to i.v. immunoglobulins.

Restless legs syndrome in spinocerebellar ataxia types 1, 2, and 3.

To identify the prevalence and determinants of restless legs syndrome (RLS) in spinocerebellar ataxia (SCA) we studied 58 patients with a molecular diagnosis of SCA1, SCA2 and SCA3. Data on the symptoms of RLS were collected by a standardized questionnaire, and RLS was diagnosed when patients met the four minimal criteria of the syndrome as recently defined by an international study group. In addition, we studied the relationship between RLS and age, age at ataxia onset, CAG repeat length, and nerve conduction and evoked potentials data. RLS was significantly more frequent in SCA patients than in controls (28% vs. 10%). Age at RLS onset in SCA was 49.0 +/- 10.9 years. There were no significant differences in nerve conduction or evoked potentials between RLS and non-RLS SCA patients. The probability of developing RLS increased with age but not with CAG repeat length or higher age of ataxia onset. The data provide evidence that patients with SCA1, SCA2 and SCA3 are per se more susceptible to RLS than non-affected individuals. The probability of developing RLS is related principally to the period over which the CAG repeat mutation exerts its effect and not to CAG repeat length or age of ataxia onset.

Autosomal dominant cerebellar ataxia type I: oculomotor abnormalities in families with SCA1, SCA2, and SCA3.

Forty-six patients suffering from autosomal dominant cerebellar ataxia type I (ADCA I) underwent to a genotype-phenotype correlation analysis by molecular genetic assignment to the spinocerebellar ataxia type 1, 2, or 3 (SCA1, SCA2, SCA3) genetic locus and electro-oculography. Oculomotor deficits that are attributed to dysfunction of cerebellar structures occurred in all three mutations without major differences between the groups. Gaze-evoked nystagmus, however, was not found to be associated with SCA2. Square wave jerks were exclusively observed in SCA3. The gain in vestibulo-ocular reflex was significantly impaired in SCA3 and SCA1. In SCA3 the severity of vestibular impairment increased with CAG repeat length. Severe saccade slowing was a highly characteristic feature of SCA2. In SCA3 saccade velocity was normal to mildly reduced while SCA1 fell into an intermediate range. The present data show that each mutation is associated with a distinct syndrome of oculomotor deficits. Reduced saccade velocity and the absence of both square-wave jerks and gaze-evoked nystagmus allow one SCA2 to be distinguished from SCA3 patients in almost all cases. The eye movement disorder of SCA1 patients, however, overlaps with both SCA2 and SCA3.

Clinical and genetic analysis of three German kindreds with autosomal dominant cerebellar ataxia type I linked to the SCA2 locus.

The detailed clinical, electrophysiological and imaging data of three German autosomal dominant cerebellar ataxia (ADCA) families are reported. Linkage to SCA2 was established using microsatellite markers D12S105, D12S1339(1328), D12S1304(1329) yielding a lod score exceeding +3.0 for the combined data. Analysis of the pedigree data provided evidence of anticipation as observed in other neurodegenerative disorders due to polyglutamine expansion encoded by a CAG repeat. This hypothesis was confirmed by the detection of the SCA2-specific pathological protein using the 1C2 monoclonal antibody which selectively recognizes large polyglutamine expansions and the characterization of a CAG expansion in the patients. Clinically, the families were characterized by progressive ataxia of stance, gait and limbs. Saccade velocity was markedly reduced in SCA2. Further oculomotor findings were gaze palsy, impaired smooth pursuit and reduced optokinetic reflex. Dementia and pyramidal tract signs were rather rare, while peripheral involvement (reduced or absent ankle reflexes, fasciculation-like movements, amyotrophy) was a prominent feature. Electrophysiological investigations provided evidence of sensory neuropathy of the axonal type and degeneration of the posterior columns. Imaging studies demonstrated severe shrinkage of brain-stem structures even in early stages of the disease.

Three-dimensional neuroanatomic images in CT-guided stereotaxic neurosurgery.

A technique is described for three-dimensional reconstruction of human diencephalic structures based on information contained in a widely used stereotaxic brain atlas. Various methods of graphically representing the obtained diencephalic volumes are discussed and examples are given. The anatomic information contained in the computerized atlas can be implemented with computed tomography performed under stereotaxic conditions. Volume data provided by the tomograms are used for three-dimensional "stretching" of the volumes presented in the atlas. Improved accuracy in identifying "invisible" diencephalic targets in functional stereotaxic neurosurgery is expected to result from this new technique.

Software balancing of multiple detectors during CT scanning.

The general requirements for balancing of detectors in a multiple detector CT scanner are discussed, and the specific requirements for software balancing using data acquired within the body section during the scan are outlined. A particular technique which can be implemented in a scanner employing a simultaneous translation and rotation of the source/detector package is presented. The technique produces an exact balancing offset and gain factors, to within accuracy limits imposed by the statistical uncertainty due to noise in the measurements. However, the technique admits a redundancy of solutions with allows the statistical sample to be expanded to include virtually all data acquired during the scan, thereby suppressing detector imbalance artifacts to the same level as overall quantum noise in the image.

Conversion of angiotensin I in isolated perfused guinea-pig and rat lung.

Increasing concentrations of angiotensin I and different perfusion rates were used to study the conversion of angiotensin I in guinea-pig and rat lungs. Even the highest concentration used (32.0 muM), which is a thousand times higher than that which occurs in vivo, was unable to saturate the converting system indicating the enormous capacity of this system. SQ 20881 proved to be a reversible inhibitor of the converting system. Its effect on the angiotensin I conversion was greater in guinea-pig lungs than in rat lungs (ID50 was 40.0 nM in guinea-pig lung and above 360.0 nM in rat lungs at a substrate concentration of 38.6 nM).

Stereotactic surgical system controlled by computed tomography.

The three-dimensional data obtained by computed tomographic (CT) scanning offer an advantage in using this imaging technique for stereotactic surgical procedures. This requires interfacing of CT image data with a stereotactic guide. In the performance of functional procedures where the surgical target must be identified from brain landmarks, such as the anterior and posterior commissures, an image reconstruction technique that presents in an image high spatial resolution structural information must be used. The description of a fully hardware- and software-interfaced CT-directed stereotactic surgical system is presented. The logic of operation and examples of images reconstructed with a high spatial resolution algorithm are illustrated. The experimentally determined measurement of an electrode tip localization with this system is within 1 pixel or +/- 0.5 mm in any direction.

Special-purpose MRI equipment for medical and industrial applications.

A brief survey of the permanent magnet design techniques that are made possible by the availability of modern magnetic materials is followed by experimental results and some consideration of their practical applicability to the realization of MRI magnets.

Facility report: New York University Imaging Science Center.

Current activity at the New York University Imaging Science Center, New York, is focused on diagnostic ultrasonographic imaging of soft tissues and computerized neurosurgery. For the latter, a new computed tomographic scanner has been designed.

[Concentration of IGF-I and estradiol-17beta in the blood plasma of pregnant cattle]. / Konzentrationen von IGF-I und Ostradiol-17 beta im Blutplasma des graviden Rindes.

Blood samples were collected from pregnant cows, heifers and also from non pregnant cows serving as controls. The determination of insulin-like-growth-factor-I (IGF-I) and estradiol-17 beta (E2) were performed immunologically. In the non pregnant cows E2 remained unchanged. IGF-I decreased around parturition and increased again commencing the 6th week of lactation. Compared to nonpregnant animals E2 but not IGF-I was slightly elevated during the first 10 weeks of pregnancy. During the 10th up to 20th week of pregnancy the mean values of IGF-I were increased as well as the ones of E2. During the late pregnancy the values of IGF-I in heifers are obviously more elevated as in lactating pregnant or non-pregnant cows; analogous high values were determined in pregnant cows only during the dry period. Before parturition even a negative correlation exists between IGF-I and E2. It is concluded that IGF-I is predominantly regulated by other factors.

Saccade velocity is reduced in presymptomatic spinocerebellar ataxia type 2.

OBJECTIVE: A characteristic feature of spinocerebellar ataxia type 2 (SCA2) is saccadic slowing at early disease stages. We sought to determine whether this sign is detectable before clinical manifestation and quantifies the disease progression throughout life in linear fashion. METHODS: In a specialized ataxia clinic, 54 presymptomatic carriers of SCA2 polyglutamine expansions and 56 relatives without mutation were documented with regard to their maximal saccade velocity (MSV). RESULTS: Among the control individuals, a significant effect of aging on MSV was observed. After elimination of this age influence through a matched-pair approach, a presymptomatic decrease of MSV could be shown. The MSV reduction was stronger in carriers of large expansions. In the years before calculated disease manifestation, the MSV impairment advanced insidiously. CONCLUSION: Saccade velocity is a sensitive SCA2 endophenotype that reflects early pontine degeneration and may be a useful diagnostic parameter before the onset of ataxia. SIGNIFICANCE: Future neuroprotective therapies of polyglutamine neurodegeneration may be assessed by MSV from earliest to prefinal disease stages.

Voxel-based morphometry and voxel-based relaxometry in multiple system atrophy-a comparison between clinical subtypes and correlations with clinical parameters.

Multiple system atrophy (MSA) is a neurodegenerative disease affecting basal ganglia, brainstem, cerebellum, and intermediolateral cell columns of the spinal cord. Clinically, a cerebellar (MSA-C) and a parkinsonian variant of MSA (MSA-P) are distinguished. We used voxel-based morphometry (VBM) and voxel-based relaxometry (VBR) in 48 MSA patients (32 MSA-C, 16 MSA-P) and 46 controls. In MSA-C, VBM revealed gray matter loss in cerebellum, right thalamus, both putamina and several cortical regions including insular cortex. Gray matter loss in the cerebellum and insular cortex was correlated with disease duration and severity. There was white matter loss in the brainstem, which was correlated with disease duration and severity. VBR analysis in MSA-C showed decreased relaxation rate R2 in cerebellum, pontine brainstem and cortical regions including insular cortex. In MSA-P, gray matter was reduced in cerebellum, dorsal midbrain, both putamina, and several cortical regions including insular cortex. A correlation with disease duration and severity was detected only for some small cortical areas. Direct comparison of MSA-C and MSA-P showed differences only in infratentorial brain regions where structural abnormalities were more pronounced in MSA-C than in MSA-P. In MSA-C, there was a stronger reduction of gray matter in the basal parts of the cerebellum, of white matter in the brainstem and of the relaxation rate R2 in the cerebellum and brainstem.