Efficacy and safety of a new bulk toxin of botulinum toxin in cervical dystonia: a blinded evaluation.

We investigated the efficacy and safety of botulinum toxin A (BTX) manufactured from a new bulk strain for the treatment of cervical dystonia. This was a single-blinded retrospective comparison of length of benefit, subjective improvement, and complications of treatment in 50 patients treated with the old form of toxin designated 79-11 and the new toxin strain BCB2024. The mean duration of benefit of the 79-11 strain and the BCB2024 strain were the same.

Convergence insufficiency in idiopathic Parkinson's disease responsive to levodopa.

We report a patient with pathologically proven idiopathic Parkinson's disease (IPD) who developed diplopia secondary to convergence insufficiency during his motor "off" periods. Diplopia resolved with onset of motor benefit from levodopa. Neuro-ophthalmologic examination demonstrated convergence insufficiency during motor "off" periods that was alleviated after onset of motor benefit from levodopa.

Evaluation of a screening questionnaire for genetic studies of Parkinson's disease.

A screening questionnaire with high sensitivity for detection of Parkinson's disease would make it easier to identify undiagnosed, yet affected, family members for genetic research. We assessed the validity of a screening questionnaire developed by Duarte et al. [1995: Mov Disord 10:643-649] with reported high specificity and sensitivity for Parkinson's disease (PD).

PET measurements of dopaminergic pathways in the brain.

Positron emission tomography (PET) measurements of dopaminergic pathways have revealed several new insights into the role of dopamine in the pathophysiology and pharmacology of brain diseases such as Parkinson's disease (PD), dystonia and schizophrenia. PET studies of regional blood flow or metabolism identifies sites of regional pathology. Drug-induced changes in flow or metabolism indicate the function of dopamine-mediated pathways.

Diminished regional cerebral blood flow response to vibration in patients with blepharospasm.

Objective: To determine whether patients with blepharospasm have abnormal sensorimotor processing similar to patients with writer's cramp.

Background: Blepharospasm is a focal dystonia manifest by involuntary, excessive blinking and squeezing of the eyes. Altered sensorimotor processing may contribute to the development of dystonic movements.

Mutation, sequence analysis, and association studies of alpha-synuclein in Parkinson's disease.

A mutation within the alpha-synuclein gene on human chromosome 4 has been reported to segregate with PD in an Italian family. We screened a sample of familial cases of PD for mutation in the alpha-synuclein gene. None of the familial cases of PD carried a mutation within the alpha-synuclein gene, and no association was detected between PD and alleles of a dinucleotide repeat marker within the alpha-synuclein gene.

Changes in brain activity during motor learning measured with PET: effects of hand of performance and practice.

The aim of this study is to assess brain activity measured during continuous performance of design tracing tasks. Three issues were addressed: identification of brain areas involved in performing maze and square tracing tasks, investigation of differences and similarities in these areas related to dominant and nondominant hand performance, and most importantly, examination of the effects of practice in these areas. A total of 32 normal, right-handed subjects were instructed to move a pen with the dominant right hand (16 subjects) or nondominant left hand (16 subjects) continuously through cut-out maze and square patterns with their eyes closed during a 40-s positron emission tomography (PET) scan to measure regional blood flow.

Levodopa responsive parkinsonism in an adult with Huntington's disease.

A patient is reported on with Huntington's disease who, as an adult, first developed severe parkinsonism with bradykinesia, rigidity, postural instability and festinating gait. His clinical signs were similar to those of the Westphal variant of Huntington's disease except that he also had resting tremor and a supranuclear gaze palsy. Magnetic resonance imaging showed caudate and putamen atrophy.

Altered thalamic response to levodopa in Parkinson's patients with dopa-induced dyskinesias.

Parkinson's disease (PD) is a progressive neurologic condition characterized by tremor, slowness, stiffness, and unstable posture. Degeneration of dopamine-producing neurons in the substantia nigra causes PD. Treatment with levodopa, a precursor of dopamine, initially ameliorates the clinical manifestations of PD.

Putamen volume in idiopathic focal dystonia.

Objective: To determine whether the volume of the putamen is abnormal in patients with idiopathic focal dystonia.

Background: The cause of adult-onset focal dystonia is unknown, but substantial evidence suggests that the putamen may be abnormal in this condition. Cell loss and gliosis have been suggested.

Mutational and biochemical analysis of dopamine in dystonia: evidence for decreased dopamine D2 receptor inhibition.

The dystonias are a group of serious movement disorders characterized by involuntary muscle spasms of different parts of the body. We recently proposed that hypofunction of dopamine D2 receptor-mediated inhibition of the indirect output pathway of the basal ganglia can result in dystonia. In this review, we discuss the results of a variety of genetic and biochemical studies in light of this hypothesis.

Preoperative treatment with botulinum toxin to facilitate cervical fusion in dystonic cerebral palsy. Report of two cases.

The authors report the use of high-dose botulinum toxin A for muscle relaxation prior to surgery for cervical spine fixation in two patients with dystonic cerebral palsy that included severe cervical dystonia. Both patients had recently developed progressive cervical myelopathy and surgery was planned to halt the insidious progressive weakness. However, marked dystonic posturing of the neck would have compromised their tolerance of halo fixation and subsequently impeded postoperative fusion.

MPTP induces dystonia and parkinsonism. Clues to the pathophysiology of dystonia.

The pathophysiology of dystonia is unclear, but several clues implicate striatal dopamine dysfunction. In contrast, the causal relationship between striatal dopamine deficiency and parkinsonism is well defined. We now suggest that parkinsonism or dystonia may occur following striatal dopamine deficiency.

Baboon basal ganglia stereotaxy using internal MRI landmarks: validation and application to PET imaging.

Purpose: We report the residual anatomic error after a nine parameter visually guided registration of MR images with a baboon brain atlas to validate a stereotactic method for use in PET studies.

Method: MPRAGE images of brain in six baboons and one nemestrina monkey were placed in atlas space using internal landmarks and proportional measurements. An expert noted the location of 23 subcortical test points in the transformed images and in the atlas.

In vivo kinetics of [18F](N-methyl)benperidol: a novel PET tracer for assessment of dopaminergic D2-like receptor binding.

A novel D2-like receptor-binding radioligand, [18F](N-methyl)benperidol ([18F]NMB), was evaluated via positron emission tomographic (PET) imaging studies of baboons. [18F]NMB rapidly localized in vivo within dopaminergic receptor-rich cerebral tissues, and striatum-to-cerebellum ratios as high as 35 were achieved after 3 hours. Pretreatment of an animal with unlabeled receptor-specific antagonists before injection of [18F]NMB confirmed that the radioligand bound specifically to central D2-like receptors in vivo, and not to S2- or D1-like receptors.

Radiation dosimetry of [18F] (N-methyl)benperidol as determined by whole-body PET imaging of primates.

Radiation absorbed doses due to IV administration of [18F](N-methyl) benperidol ([18F]NMB) were estimated by whole-body PET imaging of nonhuman primates. Time-activity curves were obtained for nine compartments (striatum, eyes, heart, lungs, liver, gallbladder, intestines, kidneys, bladder) by using dynamic PET scans of three different baboons given the radiotracer. These time-activity curves were used to calculate the residence times of radioactivity in these tissues.

PET measurement of dopamine D2 receptor-mediated changes in striatopallidal function.

This study was designed to validate an in vivo measurement of the functional sensitivity of basal ganglia neuronal circuits containing dopamine D2 receptors. We hypothesized that a D2 agonist would decrease striatopallidal neuronal activity, and hence regional cerebral blood flow (rCBF) over the axon terminals in the globus pallidus. Quantitative pallidal blood flow was measured using positron emission tomography (PET) with bolus injections of H215O and arterial sampling in six baboons before and after intravenous administration of the selective D2 agonist U91356a.

Septuagenarian Sydenham's with secondary hypomania.

A 74-year-old man with a remote history of Sydenham's chorea but no personal or family history of mood disorder had simultaneous onset of severe, generalized chorea and a mild manic syndrome in clear consciousness. Both chorea and hypomania improved after treatment with sodium valproate and clonazepam. Agitated delirium or mood lability have been described in Sydenham's, but this case is the first report of criteria-based secondary mania with probable Sydenham's chorea, as well as the longest reported remission between symptomatic Sydenham's episodes.

Decreased [18F]spiperone binding in putamen in idiopathic focal dystonia.

In this study we have investigated the pathophysiology of two idiopathic focal dystonias: hand cramp with excessive cocontractions of agonist and antagonist hand or forearm muscles during specific tasks, such as writing, and facial dystonia manifested by involuntary eyelid spasms (blepharospasm) and lower facial and jaw spasms (oromandibular dystonia). We used positron emission tomography (PET) to measure the in vivo binding of the dopaminergic radioligand [18F]spiperone in putamen in 21 patients with these two focal dystonias and compared the findings with those from 13 normals. We measured regional cerebral blood flow and blood volume in each subject as well as the radiolabeled metabolites of [18F]spiperone in arterial blood.

Dynamic changes in striatal dopamine D2 and D3 receptor protein and mRNA in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) denervation in baboons.

Loss of nigrostriatal neurons leads to striatal dopamine deficiency and subsequent development of parkinsonism. The effects of this denervation on D2-like receptors in striatum remain unclear. Most studies have demonstrated increases in striatal dopamine D2-like receptors in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-mediated denervation, but others have found either decreases or no change in binding.

A metric for testing the accuracy of cross-modality image registration: validation and application.

Purpose: Our goals were to (a) develop and validate a sensitive measure of image registration, applicable between as well as within imaging modalities; and (b) quantify the accuracy of the automated image registration (AIR) algorithm in retrospectively registering MR and PET images of baboon brain.

Method: We studied five monkeys, each with a surgically implanted "cap" that was bolted to an acrylic headholder containing fiducial markers. Anatomic MRI and PET H2 15O blood flow images were aligned using AIR (ignoring the fiducials).

Specific, reversible binding of [18F]benperidol to baboon D2 receptors: PET evaluation of an improved 18F-labeled ligand.

[18F]Benperidol ([18F]BP), a positron-emitting analogue of the dopaminergic D2 antagonist benperidol, was evaluated as a radiopharmaceutical for use with positron emission tomography (PET). PET imaging of baboons after i.v.