Susan Calne

DOUBLE-BLIND STUDY OF BOTULINUM TOXIN IN SPASMODIC TORTICOLLIS

In a double-blind trial in 21 patients with spasmodic torticollis botulinum-A toxin produced both subjective and objective improvement, including significant pain relief in 14 of the 16 patients presenting with pain. Side-effects were more frequently reported during placebo administration and no significant systemic adverse reactions were noted.

Assessment of Parkinson's Disease

The quantitative assessment of clinical deficits in Parkinsons disease has become more difficult due to such factors as the introduction of therapy that induces involuntary movements, the recognition of marked fluctuations in response to treatment, and an increasing of memory disturbance in patients. An attempt to take these problems into account using a brief and simple scale of evaluation is presented.

DCTN1 mutations in Perry syndrome

Perry syndrome consists of early-onset parkinsonism, depression, severe weight loss and hypoventilation, with brain pathology characterized by TDP-43 immunostaining. We carried out genome-wide linkage analysis and identified five disease-segregating mutations affecting the CAP-Gly domain of dynactin (encoded by DCTN1) in eight families with Perry syndrome; these mutations diminish microtubule binding and lead to intracytoplasmic inclusions. Our findings show that DCTN1 mutations, previously associated with motor neuron disease, can underlie the selective vulnerability of other neuronal populations in distinct neurodegenerative disorders.

Botulinum toxin A as treatment for drooling saliva in PD

Article abstract The authors evaluated intraparotid injections of botulinum toxin A in reducing salivary secretions and drooling in nine patients with PD. There was a marked objective reduction in secretion, and two thirds of the patients had subjective improvement in drooling. No side effects were observed. The authors conclude that botulinum toxin A promises to be a simple and effective treatment for the common problem of drooling saliva in chronic neurologic disease.

Botulinum toxin in the treatment of writer's cramp A double‐blind study

We treated 20 patients with writers cramp in a double-blind, placebo-controlled study. Each patient received two treatments in tandem, one with botulinum-A toxin (BTX-A) injections and another with normal saline, separated by 3 months. Treatment order was randomized and unknown to the patient and physician. Patients were assessed before each treatment and 2 and 6 weeks after each treatment by objective measurements of pen control. Twelve patients had improvement in pen control after treatment with BTX-A, but only four had significant improvement in writing. BTX-A injections are effective in relieving symptoms in selected cases of writers cramp, particularly in those with significant wrist-joint deviation.

Patterns of Asymmetry Do Not Change Over the Course of Idiopathic Parkinsonism Implications for Pathogenesis

Article abstract-We investigated the asymmetry of focal deficits of bradykinesia in a cross-sectional study of 198 patients with idiopathic parkinsonism. We have analyzed the difference in Unified Parkinsons Disease Rating Scale (UPDRS) scores between the more and less affected sides in these patients, whose duration of symptoms ranged from 1 to 15 years. There was no significant change in the asymmetry or focality over this period; the deficit for each side progressed faster initially and then approached the normal age-related linear rate of decline. Previous studies indicate that there is an inverse linear relation between the UPDRS bradykinesia score and the nigral dopaminergic cell count. We infer that the rate of death of nigral dopaminergic neurons is predetermined from the time of onset of pathogenesis. The simplest explanation is that a causal event kills some cells and damages others so that they undergo premature death. This sequence of changes could be implemented through environmental (toxic or viral) damage to the genome. Several diverse sources of evidence support this concept. NEUROLOGY 1995;45: 435-439

A review of normal sleep and its disturbances in Parkinson’s disease

Patients with Parkinsons disease frequently report sleep disturbances which include difficulty initiating or maintaining sleep, parasomnias or excessive daytime sleepiness. The underlying causes include: normal aging, motor symptoms of the disease, antiparkinson drugs, comorbid psychiatric conditions, and concurrent illnesses. An accurate history from the patient and care-giver regarding previous sleep patterns and how they have changed, and the degree of impact these sleep disturbances have on patients daily life is crucial for successful management. Apart from drug therapy, appropriate counselling and nonpharmacologic treatments have major roles in the overall management. This review summarizes the current concepts of (i) the pattern and function of normal sleep, and (ii) the nature, pathogenesis and management of sleep disturbances in Parkinsons disease.

Familial Parkinson's Disease: Possible Role of Environmental Factors

We report here six families with Parkinsons disease in whom the onset of symptoms tended to occur at approximately the same time irrespective of the age of the patient. The mean difference in the time of onset in different generations was 4.6 years while the mean difference in age of onset in children and parents was 25.2 years. We construe this pattern of age separation within families as suggestive of an environmental rather than genetic cause. Support for this view derives from the lack of correlation between occurrence of the disease and the degree of consanguinity. We conclude that our findings are in accord with the hypothesis which attributes the cause of some cases of Parkinsons disease to early, subclinical environmental damage followed by age-related attrition of neurons within the central nervous system.

Local Treatment of Spasmodic Torticollis with Botulinum Toxin

Fifty-six patients with spasmodic torticollis were treated with local injections of botulinum toxin. The drop out rate was 21%. The remaining 44 patients were followed for a period of 3 to 21 months. Thirty-two patients (76%) had pain relief out of 42 presenting with pain; 37 (66%) improved in the amount of sustained movements of torticollis. The efficacy was reproducible after repeated injections.

Pallidonigral TDP-43 pathology in Perry syndrome

OBJECTIVE Autosomal dominant parkinsonism, hypoventilation, depression and severe weight loss (Perry syndrome) is an early-onset rapidly progressive disease. At autopsy, previous studies have found severe neuronal loss in the substantia nigra without Lewy bodies. Transactive response DNA-binding protein of 43 kDa (TDP-43) has recently been identified as a major ubiquitinated constituent of neuronal and glial inclusions in frontotemporal lobar degeneration with ubiquitin-positive inclusions and in amyotrophic lateral sclerosis. This study reports clinical, genetic and neuropathologic investigations of Perry syndrome. METHODS Clinical data and autopsy brain tissue samples were collected from eight patients from four genealogically unrelated kindreds with Perry syndrome. Brain tissue was studied with immunohistochemistry and biochemistry for TDP-43. Patients were screened for mutations in the progranulin (GRN) and TDP-43 (TARDBP) genes. RESULTS The mean age at onset was 47 years (range 40-56), and the mean age at death was 52 years (range 44-64). In all patients, we identified TDP-43-positive neuronal inclusions, dystrophic neurites and axonal spheroids in a predominantly pallidonigral distribution, and we demonstrated changes in solubility and electrophoretic mobility of TDP-43 in brain tissue. The inclusions were highly pleomorphic and predominated in the extrapyramidal system, sparing the cortex, hippocampus and motor neurons. There were no mutations in GRN or TARDBP. INTERPRETATION Perry syndrome displays unique TDP-43 pathology that is selective for the extrapyramidal system and spares the neocortex and motor neurons.