Michael R. Swenson

Botulinum toxin type B: A double-blind, placebo-controlled, safety and efficacy study in cervical dystonia

We enrolled and treated 122 patients with idiopathic cervical dystonia in a double-blind, placebo-controlled safety and efficacy study of botulinum toxin type B (BotB). Both A-responsive and A-resistant patients were enrolled. Patients received intramuscular injections of either BotB (2,500 U, 5,000 U, or 10,000 U) or placebo. The primary outcome measure of efficacy was the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-Total score at 4 weeks following study drug administration. Secondary measures of efficacy were TWSTRS-Severity, -Disability, and -Pain subscale scores, and Analog Pain Assessment, Investigator Global Assessment, Patient Global Assessment, and Sickness Impact Profile scores. Duration of effect was estimated with an intent-to-treat analysis of responders. Safety measures included clinical parameters, laboratory tests, and adverse events. The primary and most of the secondary analyses indicated a statistically significant treatment effect and a dose response. BotB is safe, well tolerated, and efficacious in the treatment of cervical dystonia at the doses tested.

Dissociations within nondeclarative memory in Huntington's disease.

Patients with Huntingtons Disease (HD) were tested on 2 tasks, probabilistic classification learning and artificial grammar learning. Both tasks are performed normally by amnesic patients and are considered to be independent of declarative memory. Patients with HD were severely impaired in probabilistic learning but performed normally in artificial grammar learning. The probabilistic classification task may be akin to habit-learning tasks that depend on the neostriatum, whereas artificial grammar learning may depend on changes within neocortex similar to what is thought to occur in perceptual priming. The deficit in the probabilistic classification task indicates that impaired nondeclarative learning in patients with HD occurs not only in motor tasks but also in nondeclarative learning tasks that have no motor component. Huntingtons disease (HD) is an inherited progressive neurological disorder that is characterized by involuntary, choreiform movements, affective disturbance, and progressive cognitive and functional decline. The primary neuropathology

Comparison of botulinum toxin serotypes A and B for the treatment of cervical dystonia

Objective: To directly compare two serotypes of botulinum toxin (BoNTA and BoNTB) in cervical dystonia (CD) using a randomized, double-blind, parallel-arm study design. Methods: Subjects with CD who had a previous response from BoNTA were randomly assigned to BoNTA or BoNTB and evaluated in a blinded fashion at baseline, 4 weeks, 8 weeks, and 2-week intervals thereafter until loss of 80% of clinical effect or completion of 20 weeks of observation. CD severity was measured with the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS), and adverse events were assessed by structured interview. Statistical analysis included Wilcoxon rank sum test, log rank tests, and Kaplan–Meier survival curves for duration of effect. Results: A total of 139 subjects (BoNTA, n = 74; BoNTB, n = 65) were randomized at 19 study sites. Improvement in TWSTRS score was found at 4 weeks after injection and did not differ between serotypes. Dysphagia and dry mouth were more frequent with BoNTB (dysphagia: BoNTA 19% vs BoNTB 48%, p = 0.0005; dry mouth (BoNTA 41% vs BoNTB 80%, p < 0.0001). In clinical responders, BoNT A had a modestly longer duration of benefit (BoNTA 14 weeks, BoNTB 12.1 weeks, p = 0.033). Conclusion: Both serotypes of botulinum toxin (BoNTA and BoNTB) had equivalent benefit in subjects with cervical dystonia at 4 weeks. BoNTA had fewer adverse events and a marginally longer duration of effect in subjects showing a clinical response.

EFFECTS OF ACUTE, GRADED COMPRESSION ON SPINAL NERVE ROOT FUNCTION AND STRUCTURE : AN EXPERIMENTAL STUDY OF THE PIG CAUDA EQUINA

A well-controlled experimental model for analysis of compression-induced functional changes of the porcine cauda equina is presented. The model allows for electrophysiologic investigation of a variety of neurophysiologic changes induced by nerve root deformation. At an acute pressure threshold of 50-75 mm Hg, changes in both afferent and efferent conduction are induced. With higher compression pressure, a differential recovery in afferent and efferent conduction is seen.

Cerebrovascular complications of L‐asparaginase therapy

L-Asparaginase, commonly used in combination chemotherapy in the treatment of acute lymphoblastic leukemia, has been associated with hemorrhagic and thrombotic cerebrovascular events. Thrombosis of the cerebral veins or dural sinuses is common, and may be associated with either hemorrhage or infarction. This syndrome generally occurs after a few weeks of therapy, and may occur after L-asparaginase therapy is completed. Complications appear to result from depletion of plasma proteins involved in coagulation and fibrinolysis. We now report two additional cases of cerebrovascular complications associated with L-asparaginase therapy. We review the previously reported cases and discuss the clinical presentation, pathophysiology, and suggested treatment of this syndrome.

Preservation of evoked potentials in a case of anterior spinal artery syndrome.

A case of anterior spinal artery syndrome is presented for which there are neurologic, electrophysiologic, and pathologic correlations. Ten days prior to her death, a 52-year-old hypertensive female developed severe chest pain and lower extremity weakness. A diagnosis of aortic dissection resulting in an anterior spinal artery syndrome was made. Intraoperative posterior tibial somatosensory evoked potentials demonstrated normal morphology and latencies. Autopsy revealed an infarction of the anterior portion of the thoraco-lumbar spinal cord with preservation of the posterior columns. This case demonstrates that severe spinal cord injury can exist in the presence of preserved somatosensory evoked potentials.

Effects of magnitude and duration of compression on spinal nerve root conduction

Spinal nerve root compression occurs commonly in conditions such as herniated nucleus pulposus, spinal stenosis, and trauma. However, the pathophysiology of the symptoms and signs related to spinal nerve root compression is poorly understood. The purpose of the present study was to assess and compare effects of various pressures and durations of acute compression on spinal nerve root conduction in the pig cauda equina. Efferent conduction (compound motor action potentials) and afferent conduction (compound nerve action potentials) were monitored during compression for 2 or 4 hours with compression pressures of 0 (sham), 50,100, or 200 mm Hg. Recovery from compression was monitored for 1.5 hours. No significant deficits in spinal nerve root conduction were observed with 0 or 50 mm Hg compression, compared to significant conduction deficits induced by 100 and 200 mm Hg compression. Three–way analysis of variance demonstrated significant effects of compression pressure and duration on conduction at the end of compression and recovery, with a significant difference between efferent and afferent conduction at the end of the recovery period. These observations suggest an interaction between biomechanical and microvascular mechanisms in the production of nerve root conduction deficits. Such information may relate to the motor and sensory dysfunction in clinical conditions associated with spinal nerve root compression.

Predictors of nursing home placement in Huntington disease

Objective: To determine whether motor, behavioral, or psychiatric symptoms in Huntington disease (HD) predict skilled nursing facility (SNF) placement. Methods: Subjects were participants in the Huntington Study Group’s Unified Huntington Disease Rating Scale Database (Rochester, NY) between January 1994 and September 1999. Specific motor, psychiatric, and behavioral variables in subjects residing at home and in SNF were analyzed using χ2 and Student’s t-tests. For a subset of subjects for whom longitudinal data existed, a Cox proportional hazards model controlling for age, sex, and disease duration was used. Results: Among 4,809 subjects enrolled, 3,070 had clinically definite HD. Of these, 228 (7.4%) resided in SNF. The SNF residents’ average age was 52 years, average disease duration was 8.6 years, and they were predominantly women (63%). The SNF residents had worse motor function (chorea, bradykinesia, gait abnormality, and imbalance, p < 0.0001); were more likely to have obsessions, compulsions, delusions, and auditory hallucinations; and had more aggressive, disruptive (p < 0.0001), and irritable behaviors (p = 0.0012). For 1,559 subjects, longitudinal data existed (average length of follow-up, 1.9 years), and 87 (5%) moved from home to SNF. In the Cox model, bradykinesia (HR 1.965, 95% CI 1.083 to 3.564), impaired gait (HR 3.004, 95% CI 1.353 to 6.668), and impaired tandem walking (HR 2.546, 95% CI 1.460 to 4.439) were predictive of SNF placement. Conclusions: Institutionalized patients with HD are more motorically, psychiatrically, and behaviorally impaired than their counterparts living at home. However, motor variables alone predicted institutionalization. Treatment strategies that delay the progression of motor dysfunction in HD may postpone the need for institutionalization.

Effects of botulinum toxin therapy in patients with adductor spasmodic dysphonia: Acoustic, aerodynamic, and videoendoscopic findings

Botulinum toxin has been previously reported to be successful in the treatment of spasmodic dysphonia. To objectively document results, 11 patients with adductor spasmodic dysphonia who received unilateral treatment of the thyroarytenoid muscle were studied. Acoustic analyses and airflow rates during sustained phonation and flexible videoendoscopy were performed prior to, 1 week and 1 month after injection. 1. Acoustic parameters demonstrated significant voice improvement, although abnormal characteristics remained. 2. Mean airflow rates were increased 1 week after injection with almost normal values 1 month later. 3. Videolaryngoscopy showed an effective reduction of intrinsic laryngeal muscle hyperfunction with less effect on extrinsic muscle activity. Interrelations between videolaryngoscopic rating scores, acoustic results and aerodynamic results are discussed.

Distinct cognitive profiles of cortical and subcortical dementia in advanced illness

Article abstract—We administered the Mattis Dementia Rating Scale (DRS) to 120 patients to evaluate the effect of dementia severity on distinct cognitive profiles. Sixty patients with Huntingtons disease (HD) and 60 patients with Alzheimers disease (AD) were separated by dementia severity into three groups: mildly demented (DRS mean total = 129), moderately demented (DRS mean total = 117), and severely demented (DRS mean total = 102). At all levels of dementia severity, HD patients demonstrated greater impairment than AD patients on the Initiation/Perseveration sub-scale, whereas AD patients demonstrated greater impairment than HD patients on the Memory subscale. At moderate and severe levels of dementia, HD patients demonstrated an additional impairment in constructional praxis. These profile differences were independent of dementia severity and continued to differentiate between so-called cortical and subcortical dernentias in later stages of dementia severity.