A randomized, double-blind, placebo-controlled study of the efficacy and safety of botulinum toxin type A in upper limb spasticity in patients with stroke.

OBJECTIVE: To study the efficacy and safety of botulinum toxin type A (BtxA) in the treatment of upper limb muscle spasticity, caused by stroke. METHODS: This was a randomized, controlled trial. Patients received either placebo injections or a total of 1000 IU of BtxA (Dysport) into five muscles of the affected arm. Muscle tone was assessed using the Modified Ashworth Scale (MAS). Other outcome measures were the change in the joint range of motion (ROM), the Barthel index, pain score, goal attainment and the subjective evaluation of benefit by patients and investigators. The patients were assessed blind to randomization at baseline and 4, 8, 12 and 16 weeks after treatment. RESULTS: Fifty nine patients were recruited and received treatment. One patient was lost to follow-up before the last scheduled visit of the study. The group of patients who received BtxA had a significant reduction in the summed MAS score at week 4 compared with the placebo group (P=0.004). The magnitude of benefit over the 16 week follow-up period was significantly reduced for the BtxA group in the wrist (P=0.004) and the finger joints (P=0.001) when compared with the placebo. There was no statistically significant difference between the groups in the joint ROM, muscle pain, goal-attainment or the Barthel index scores at week 4 of the study. At week 16, the BtxA group showed significantly greater improvement in the passive ROM at the elbow (P=0.036). The patients' global assessment of benefit at the end of the study showed that 16 (50%) patients in the placebo group had 'much improved' or had 'some improvement' compared with 24 (92.3%) patients in the BtxA group (P=0.007). The investigators' rating for the same item was 16 (50%) and 23 (88.4%) patients, respectively (P=0.002). Sixteen and twenty patients in the BtxA and placebo groups, respectively, had an adverse event. The most frequently reported adverse events were accidental injury, respiratory and urinary tract infections and muscle pain. CONCLUSION: The findings of the present study suggest that treatment with BtxA in a dose of 1000 units reduces muscle tone in patients with post-stroke upper limb spasticity. This effect is sustained for at least 16 weeks. BtxA is safe in the dose used in this study. IMPORTANT NOTE: The authors wish to emphasize that the botulinum toxin preparation used in this study was Dysport (Ipsen Ltd) which has a different therapeutic equivalence from other commercially available product, Botox (Allergan Inc.).

[Hypokalemic paralysis in furosemide therapy and simultaneous laxative abuse]. / Dyskaliämische Lähmung bei Furosemidtherapie und gleichzeitigem Laxanzienabusus.

BACKGROUND: Clinical signs of hypokalemia are not directly related to the extent of the electrolyte imbalance, and therefore monosymptomatic cases may be observed. CASE REPORT: Following an acute gastroenteritis with considerable diarrhea, a 47-year-old male patient was admitted to hospital for progressive painful paraparesis. Upon admission, the patient complained of painful paresthesias in both legs, and a moderate flaccid paraparesis with widespread fasciculations and loss of leg tendon reflexes was found. Serum potassium level on admission was 1.7 mmol/l. Other signs of hypokalemia were absent, and the ECGs showed a slow sinus rhythm without disturbances of de- or repolarisation or cardiac arrhythmias. Hypokalemic paralysis was diagnosed and was considered to be primarily drug-induced, as the patient had a history of laxative abuse and was on a continuous medication with furosemide (80 mg/d) without regular assessment of serum electrolytes. The additional electrolyte loss following the gastroenteritis precipitated the development of clinical signs of hypokalemia. In parallel to the rise in serum potassium levels, both painful paresthesias and muscle weakness disappeared, and electromyography documented the amelioration of the myopathic syndrome. CONCLUSION: The prominent clinical symptom of hypokalemia was a dyskalemic paralysis in the absence of other sequelae of electrolyte imbalance, such as cardiac arrhythmias or vegetative disturbances.

Function of the cerebellum in Parkinsonian rest tremor and Holmes' tremor.

We describe a patient who developed Parkinson's disease (PD) 17 years after resection of his right cerebellum because of a Lindau tumor. He showed a classic 4.3-Hz resting tremor on the left side but a 3.1-Hz resting, postural, and intention tremor on the right side compatible with midbrain tremor (Holmes' tremor). We conclude that the generator of the tremor in PD cannot be located within the olivocerebellar loop. The cerebellum, however, seems to modulate the tremor frequency of parkinsonian rest tremor and may prevent the rest tremor from transforming into a postural and goal-directed tremor.

[Value of functional imaging in Parkinson's disease and related movement disorders]. / Möglichkeiten und Grenzen funktioneller bildgebender Verfahren beim Parkinson-Syndrom.

Modalities for imaging morphology do not contribute significantly to the differential diagnosis of movement disorders. In contrast, functional imaging as PET or SPECT can differentiate among Parkinson's disease (PD), vascular or toxic Parkinsonism and movement disorders within multi system degeneration. Especially the decreased DOPA uptake--detected by 18F-DOPA or 123I-beta CIT--within the striate with accentuation in the posterior putamen is typical for PD, where initially D2-receptor activity--imaged by 11C-raclopride or 123I-iodobenzamide--is increased. In contrast to this typical pattern dopaminergic terminals as well as D2-receptors are diffusely reduced in multi system degeneration, where often energy metabolism is additionally disturbed. In Parkinson syndrome of vascular origin focal disturbances of pre- and postsynaptic dopaminergic sites and energy metabolism are found, movement disorders after intoxication are accompanied by selective loss of dopaminergic neurons (MPTP) or by widespread neuronal damage in the basal ganglia as well as in the cortex (Cyanide, solvents). Functional studies additionally permit the follow-up of disease progression, by which also the efficacy of therapeutic strategies can be assessed.

[Mycotic aneurysm in endocarditis lenta as the etiology of intraparenchymatous cerebral hemorrhage]. / Mykotisches Aneurysma bei Endocarditis lenta als Ursache für intraparenchymatöse Hirnblutung.

CASE REPORT: A 49-year-old male was admitted for left-side headache and mild speech defect. Clinical examination showed a pansystolic murmur of mitral regurgitation and mild Wernicke aphasia. In laboratory studies ESR and CRP were increased. Computed tomography of brain revealed a left temporoparietal hematoma. Echocardiographic examination demonstrated vegetations and mitral valve perforation. In blood cultures grew alpha-streptococci. Cerebral angiography was performed and a fusiform aneurysm on a distal branch of the left middle cerebral artery was identified. Follow-up angiography showed a total resolution of the aneurysm after 6 weeks of intravenous antibiotics. CONCLUSION: This case demonstrate that patients with intracerebral hematomas associated with infectious endocarditis should be investigated for mycotic intracranial aneurysm.

Functional effects of striatal dysfunction in Parkinson disease.

BACKGROUND: Concepts of basal ganglia organization suggest structually and functionally segregated pathways that link putamen and caudate function to motor and cognitive performance, respectively. OBJECTIVE: To investigate whether motor and cognitive impairment in Parkinson disease is attributable to selective disturbance in nigrostriatal, dopaminergic function and regional cerebral glucose metabolism. DESIGN: Twenty patients with probable Parkinson disease underwent positron emission tomographic measurements of dopaminergic, nigrostriatal function (positron emission tomography with fluorodopa F 18), regional glucose metabolism (positron emission tomography with fludeoxyglucose F 18), memory testing, and evaluation of locomotor disability. RESULTS: Memory performance in the patient cohort strongly correlated with the individual disease duration and degree of locomotor disability (P < .05). Striatal uptake rates of fluorodopa F 18 were significantly reduced in all patients (P < .05) compared with those in normal control subjects, and putaminal rates correlated significantly with the patients' degree of locomotor disability (P < .01) but not with memory performance. In the patients with an advanced stage of disease, there was a significant correlation between reduced caudate uptake rates of fluorodopa F 18 and the patients' impairment in delayed recall performance of the memory task (P < .05) but not with the individual degree of locomotor disability. No changes were found for regional glucose metabolic rates in the patients compared with the controls. CONCLUSIONS: The present study provides evidence for the hypothesis that on the level of the striatum, motor impairment in Parkinson disease may be assigned to altered dopamine neuronal integrity in the putamen but not in the caudate, whereas memory impairment in the more advanced cases may be attributed to caudate but not putaminal dysfunction.

11C-methionine and 18F-2-fluorodeoxyglucose positron emission tomography: a tool for diagnosis of cerebral glioma and monitoring after brachytherapy with 125I seeds.

Forty-six patients with suspected brain tumors were investigated by positron emission tomography (PET). Using 11C-methionine PET, the spatial extent of increased uptake in gliomas was larger than that of contrast enhancement on CT/MR images in 67% or the same in 33%. Ten of 46 patients treated with brachytherapy for low-grade gliomas were also investigated with 18F-2-fluorodeoxyglucose (FDG)-PET. One year after seed implantation, the glucose metabolism had not changed, but the decline of methionine uptake was significant. In conclusion, 11C-methionine PET may improve tumor delineation and, following brachytherapy, provides more information on the therapeutic effects than FDG.

Glucose consumption and methionine uptake in low-grade gliomas after iodine-125 brachytherapy.

We investigated whether 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) and carbon-11 methionine are suitable tracers to monitor the effects of therapy for low-grade gliomas. Ten patients with low-grade glioma without previous treatment were studied with FDG positron emission tomography. Additionally, l-[methyl-11C]methionine uptake was measured in five subjects before and 1 year after computerized tomography (CT)-guided stereotactic and computer-assisted implantation of iodine-125 seeds. All scans were 3D-matched to CT, isodose volumes were determined, and changes in glucose metabolism and methionine uptake were evaluated in tumour and brain tissue as a function of radiation dose. After 1 year glucose metabolism was not significantly altered up to a radiation dose of 300 Gy, whereas methionine uptake showed a significant dose-dependent decrease. Higher rates of decline were found in tumours with high basal methionine incorporation activity before therapy. These data suggest that measurement of methionine uptake is more suitable than measurement of FDG uptake for monitoring therapeutic effects in low-grade gliomas.

Diaschisis of specific cerebellar lobules: pontine haematoma studied with high-resolution PET and MRI.

Cerebellar glucose metabolism was studied in one patient with a hemipontine haematoma in order to investigate remote metabolic effects within the cerebellar lobules. In the patient, who suffered a circumscribed hemipontine haemorrhage, and in three normal subjects cerebellar glucose metabolisms was studied using 18F-2-fluoro-2-deoxy-D-glucose and high-resolution positron emission tomography (PET). Regions of interest were placed on sagittal brain slices of co-registered magnetic resonance images for quantitative evaluation of glucose metabolism in each cerebellar lobule. Interruption of corticopontine fibres caused inactivation of pontine nuclei with subsequent contralateral cerebellar diaschisis, mainly in the anterior lobe and the posterior portion of the quadrangular lobule. Damage within the ponto-cerebellar part of the cortico-ponto-cerebellar pathway, e.g. pontine nuclei and crossing ponto-cerebellar fibres from contralateral pontine nuclei, led to ipsi- and contralateral cerebellar diaschisis within the semilunar, gracile and biventral lobules. High-resolution PET is capable of demonstrating bilateral diaschisis involving specific cerebellar lobules to a different degree that is consistent with the pontine anatomy of the cortico-ponto-cerebellar pathway and with the location of the haemorrhagic lesion.

Planum temporale and Brodmann's area 22. Magnetic resonance imaging and high-resolution positron emission tomography demonstrate functional left-right asymmetry.

OBJECTIVE: To describe the registered analysis of magnetic resonance imaging and glucose metabolic data acquired with positron emission tomography to determine the relationship between structure and function of temporal lobe cortical structures between the left and right hemispheres. BACKGROUND: The dominance of the left cerebral hemisphere is associated with a preponderance of the left planum temporale. SUBJECTS AND METHODS: Fifteen subjects without signs or symptoms of a neurological disorder. Three-dimensional-registered magnetic resonance imaging and positron emission tomography with the use of fludeoxyglucose F18 and a high-resolution positron emission tomography scanner. Analysis of regional metabolic activation during single-word repetition on matched parasagittal magnetic resonance imaging and positron emission tomography. RESULTS: The planum temporale was bilaterally activated without left-right asymmetry. The metabolic increase was asymmetric within the left Brodmann's area (BA) 22. The part of the left BA 22 that was buried in the superior temporal sulcus was significantly less activated than the part of BA 22 on the surface of the superior temporal gyrus. The metabolic activation in the sulcal part of the left BA 22 had a significant inverse correlation with the anatomical predominance of the left planum temporale (r = .71, P = .003) and a significant direct correlation with the metabolic activation in the surface aspects of the right BA 22 (r = .82, P < .001). CONCLUSION: Brodmann's area 22 is a critical feature of language dominance and is also important with regard to the exchange of information between the two hemispheres.

An interactive technique for three-dimensional image registration: validation for PET, SPECT, MRI and CT brain studies.

UNLABELLED: A multipurpose three-dimensional registration technique was validated with PET, SPECT, CT and MRI scans, which had been obtained under normal clinical conditions. In contrast to fully automated procedures, this coregistration method is highly interactive, which has the advantage that it does not impose rigid restrictions by data type and by alterations in normal anatomy or brain function resulting from disease. METHODS: Basically, a computer program provides a variety of tools to examine the accuracy of coregistration visually and to specify necessary translations and rotations in all three dimensions. Tools and criteria to accept coregistration were applied according to a standardized protocol. Reproducibility was assessed with five independent users on nine pairs of image sets. In two pairs of these image sets, coregistration was repeated three times by each user. RESULTS: Depending on the resolution of the images involved, the reproducibility of translation distances ranged from 0.32 to 2.22 mm (s.d.) and of rotation angles from 0.32 to 1.70 degrees. It was always much smaller than the point-spread full-width half maximum of the device with the lower resolution. The accuracy of coregistration was examined using two arbitrarily misplaced image sets. Interindividual and intraindividual variance were similar, which suggested that the influence of subjectivity was not significant. Average displacements after coregistration were 0.43 and 0.29 mm or less for PET and MRI data, respectively, which indicated the absence of a systematic bias. CONCLUSION: The results indicate the high reproducibility and accuracy of this three-dimensional coregistration technique, which is comparable or superior to those of automated techniques and methods based on external artificial landmarks.

Individual metabolic anatomy of repeating words demonstrated by MRI-guided positron emission tomography.

The anatomical localization of brain areas involved in repeating words was examined in six right-handed non-aphasic subjects. Their individual metabolic activation was studied with positron emission tomography (PET) and [18F]2-fluoro-2-deoxy-D-glucose (FDG) using a new data processing technique that includes three-dimensional coregistration with magnetic resonance images. Left superior temporal gyrus (cortical convexity surface, Brodmann area 22), right superior temporal lobe (superior temporal sulcus and bottom of transverse sulcus), sensorimotor cortex (vocalization area) bilaterally, and supplementary motor cortex were consistently activated in each individual. Cerebellar activation was more variable. In contrast to previous blood flow activation studies with averaging across subjects, this new technique permits the anatomical localization and quantitation of activated areas in each individual. It can therefore also be applied to patients with brain lesions.

The amygdala's contribution to memory--a study on two patients with Urbach-Wiethe disease.

The consequences of primary amygdaloid damage on memory performance are described in terms of neuropsychological, CT, MRI and PET results of two patients, a brother and a sister. Both had circumscribed, bilaterally symmetrical damage confined to the amygdaloid region, while the hippocampal formation and other brain structures were intact. PET-imaging furthermore revealed an overall decrease in glucose metabolism which was particularly apparent at the cingular and thalamic levels. Although neither patient was amnesic, both showed memory impairments in selective tests. In one patient these impairments were more pronounced and they were accompanied by marked affective-emotional fluctuations. Our results suggest that the amygdaloid region is a bottle-neck structure that confers an affective flavour to memories, thereby enhancing the probability of their long term storage.

Type of fimbriation determines adherence of Klebsiella bacteria to human epithelial cells.

Clinical isolates of three Klebsiella strains (encapsulated and nonencapsulated mutants) with type 1 (mannose-sensitive, MS+MR-), type 3 (mannose-resistant, MS-MR+) and type 1 and 3 (MS+MR+) fimbriae were investigated for their ability to adhere to epithelial cells. Considerable adhesion to human buccal, tracheal, pulmonary and uroepithelial cells could be demonstrated. Independent of encapsulation and type of epithelial cells, adhesion of MS+MR+ (type 1.3) fimbriated Klebsiella bacteria was significantly stronger than adhesion of microorganisms carrying only type 1 (MS+MR-) or type 3 (MS-MR+) fimbriate, respectively. Adherence of nonencapsulated type 1 and 3 (MS+MR+) fimbriated Klebsiella bacteria to mammalian cells was significantly inhibited in the presence of D-mannose. Certain carbohydrates (D-glucose, D-galactose) did not interfere with this adhesion process.