Botulinum toxin (BoNT) is highly effective in the treatment of cervical dystonia (CD), yet a significant proportion of patients report low levels of satisfaction following treatment and fail to follow up for repeated treatments. The goal of this study was to determine the reasons that some patients have unsatisfactory responses. A total of 35 subjects who came to our center requesting alternative treatments due to unsatisfactory responses following BoNT treatment for CD were evaluated. Included were 26 women and 9 men with an average age of 57.1 years (range 25–82 years), and an average duration of illness of 12.5 years (range 1–55 years). Details of unsatisfactory BoNT treatments were methodically collected by a movement specialist using a standardized intake form, including provider subspecialty, product used, the number of satisfactory or unsatisfactory trials, doses given, specific muscles treated, the use of electromyographic guidance, side effects, and tests of resistance. The specialist then provided repeat treatments if indicated, and followed each case until the reasons for unsatisfactory outcomes could be determined. Multiple reasons for unsatisfactory outcomes were found. They included suboptimal BoNT doses, suboptimal muscle targeting, intolerable side effects, complex movement patterns, discordant perceptions, and incorrect diagnoses. Only one patient was functionally resistant to BoNT. Of 32 subjects who received repeat BoNT treatments, 25 (78 %) achieved satisfactory responses after revision of the original treatment plan. These results indicate that the majority of unsatisfactory responses to BoNT treatment of CD were caused by correctible factors and imply a need for improved education regarding optimal treatment methods.
Cervical dystonia (CD) is a neurological disorder characterized by abnormal movements and postures of the head. The brain regions responsible for these abnormal movements are not well understood, because most imaging techniques for assessing regional brain activity cannot be used when the head is moving. Recently, we mapped brain activation in healthy individuals using functional magnetic resonance imaging during isometric head rotation, when muscle contractions occur without actual head movements. In the current study, we used the same methods to explore the neural substrates for head movements in subjects with CD who had predominantly rotational abnormalities (torticollis). Isometric wrist extension was examined for comparison. Electromyography of neck and hand muscles ensured compliance with tasks during scanning, and any head motion was measured and corrected. Data were analyzed in three steps. First, we conducted within-group analyses to examine task-related activation patterns separately in subjects with CD and in healthy controls. Next, we directly compared task-related activation patterns between participants with CD and controls. Finally, considering that the abnormal head movements in CD occur in a consistently patterned direction for each individual, we conducted exploratory analyses that involved normalizing data according to the direction of rotational CD. The between-group comparisons failed to reveal any significant differences, but the normalization procedure in subjects with CD revealed that isometric head rotation in the direction of dystonic head rotation was associated with more activation in the ipsilateral anterior cerebellum, whereas isometric head rotation in the opposite direction was associated with more activity in sensorimotor cortex. These findings suggest that the cerebellum contributes to abnormal head rotation in CD, whereas regions in the cerebral cortex are involved in opposing the involuntary movements.
Background Dystonia is a neurological disorder characterized by involuntary twisting movements and postures. The neck is among the most commonly affected regions, and diagnosis can be made readily through a simple clinical evaluation. The goal of this study was to explore how long it took patients to receive a diagnosis of cervical dystonia after symptom onset. Methods A structured questionnaire was administered at outpatient clinics of a tertiary care academic medical center to 146 consecutively evaluated patients. The questionnaire addressed the length of time from symptom onset to diagnosis, the numbers and types of providers seen before reaching a diagnosis, and treatments attempted prior to receiving botulinum toxin. Results A total of 108 patients saw a mean of 3.5 providers over a mean period of 44 months from symptom onset to diagnosis. For patients with symptom onset in the last decade only, patients saw a mean of 3.0 providers over a mean of 14 months. Conclusions Although cervical dystonia is the most common form of dystonia with clinical features readily identifiable by a simple history and examination, patients typically see multiple providers over more than a year before reaching a diagnosis and receiving optimal therapy. Improved awareness of the clinical features will enable patients to obtain appropriate therapy more rapidly.
Background: Previous studies have demonstrated both clinical and neurochemical similarities between Parkinson’s disease (PD) and narcolepsy. The intrusion of REM sleep into the daytime remains a cardinal feature of narcolepsy, but the importance of these intrusions in PD remains unclear. In this study we examined REM sleep during daytime Maintenance of Wakefulness Testing (MWT) in PD patients.
Methods: Patients spent 2 consecutive nights and days in the sleep laboratory. During the daytime, we employed a modified MWT procedure in which each daytime nap opportunity (4 per day) was extended to 40 minutes, regardless of whether the patient was able to sleep or how much the patient slept. We examined each nap opportunity for the presence of REM sleep and time to fall asleep.
Results: Eleven of 63 PD patients studied showed 2 or more REM episodes and 10 showed 1 REM episode on their daytime MWTs. Nocturnal sleep characteristics and sleep disorders were unrelated to the presence of daytime REM sleep, however, patients with daytime REM were significantly sleepier during the daytime than those patients without REM. Demographic and clinical variables, including Unified Parkinson’s Disease Rating Scale motor scores and levodopa dose equivalents, were unrelated to the presence of REM sleep.
Conclusions: A sizeable proportion of PD patients demonstrated REM sleep and daytime sleep tendency during daytime nap testing. These data confirm similarities in REM intrusions between narcolepsy and PD, perhaps suggesting parallel neurodegenerative conditions of hypocretin deficiency.
Background
Many patients with idiopathic Parkinson’s disease experience difficulties maintaining daytime alertness. Controversy exists regarding whether this reflects effects of anti-Parkinsonian medications, the disease itself or other factors such as nocturnal sleep disturbances. In this study we examined the phenomenon by evaluating medicated and unmedicated Parkinson’s patients with objective polysomnographic measurements of nocturnal sleep and daytime alertness.
Methods
Patients (n = 63) underwent a 48-hour laboratory-based study incorporating 2 consecutive nights of overnight polysomnography and 2 days of Maintenance of Wakefulness Testing. We examined correlates of individual differences in alertness, including demographics, clinical features, nocturnal sleep variables and class and dosage of anti-Parkinson’s medications.
Results
Results indicated that: 1) relative to unmediated patients, all classes of dopaminergic medications were associated with reduced daytime alertness and this effect was not mediated by disease duration or disease severity; 2) increasing dosages of dopamine agonists were associated with less daytime alertness, whereas higher levels of levodopa were associated with higher levels of alertness. Variables unrelated to Maintenance of Wakefulness Test defined daytime alertness included age, sex, years with diagnosis, motor impairment score and most nocturnal sleep variables.
Conclusions
Deficits in objectively assessed daytime alertness in Parkinson’s disease appear to be a function of both the disease and the medications and their doses utilized. The apparent divergent dose-dependent effects of drug class in Parkinson’s disease are anticipated by basic science studies of the sleep/wake cycle under different pharmacological agents.
Introduction: Cervical dystonia is the most common of the adult-onset focal dystonias. Most cases are idiopathic. The current view is that cervical dystonia may be caused by some combination of genetic and environmental factors. Genetic contributions have been studied extensively, but there are few studies of other factors. We conducted an exploratory metabolomics analysis of cervical dystonia to identify potentially abnormal metabolites or altered biological pathways. Methods: Plasma samples from 100 cases with idiopathic cervical dystonia and 100 controls were compared using liquid chromatography coupled with mass spectrometry-based metabolomics. Results: A total of 7346 metabolic features remained after quality control, and up to 289 demonstrated significant differences between cases and controls, depending on statistical criteria chosen. Pathway analysis revealed 9 biological processes to be significantly associated at p < 0.05, 5 pathways were related to carbohydrate metabolism, 3 pathways were related to lipid metabolism. Conclusion: This is the first large scale metabolomics study for any type of dystonia. The results may provide potential novel insights into the biology of cervical dystonia.
The underlying etiology of parkinsonian anterocollis has been the subject of recent debate. The purpose of this study is to test the hypothesis that anterocollis in parkinsonian syndromes is associated with dystonia of the deep cervical flexors (longus colli and capitis). Eight patients with anterocollis, six in the setting of parkinsonism and two primary cervical dystonia control subjects with anterocollis underwent prospective structured clinical evaluations (interview, examination and rating scales), systematic electromyography of the cervical extensor musculature and 18F-FDG PET/CT studies of cervical muscles to examine evidence of hypermetabolism or overactivity of deep cervical flexors. Subjects with parkinsonian anterocollis were found to have hypermetabolism of the extensor and sub-occipital muscles but not in the cervical flexors (superficial or deep). EMG abnormalities were observed in all evaluated patients, but only one patient was definitely myopathic. Meanwhile, both dystonia controls exhibited hypermetabolism of cervical flexors (including the longus colli). In conclusion, we were able to demonstrate hypermetabolism of superficial and deep cervical flexors with muscle 18F-FDG PET/CT in dystonic anterocollis patients, but not in parkinsonian anterocollis patients. The hypermetabolic changes seen in parkinsonian anterocollis patients in posterior muscles may be compensatory. Alternative explanations for anterocollis include myopathy of the cervical extensors, or unbalanced rigidity of the cervical flexors, but this remains to be proven.
OBJECTIVE: To examine the nature of the association between affective disorders and psychosis in Parkinson's disease (PD). BACKGROUND: In PD, psychosis and affective disorders are common and independently impact quality of life and mortality. Both depression and psychosis are correlated with the occurrence of cognitive dysfunction, suggesting that they may share neurobiological substrates. Anxiety has not been examined as a correlate of psychosis. METHODS: 144 PD subjects were evaluated with the Schedule for Assessment of Positive Symptoms to assess psychotic features, while depression and anxiety were examined by the Structured Clinical Interview for DSM-IV-TR (SCID) and self-assessment scales Beck Depression Inventory II (BDI-II) and Beck Anxiety Inventory (BAI). Correlational analyses assessed associations between hallucinations and delusions with depression and anxiety. RESULTS: A diagnosis of anxiety (SCID) was significantly (p=.015) associated with hallucinations (OR=4.81, CI=1.36-16.99). Severity of anxiety (BAI) significantly predicted (p=.03) the presence of hallucinations (OR=1.08, CI=1.01-1.15) and delusions (OR=1.09, CR=1.01-1.17). Current depression (SCID) was significantly (p=.001) associated with the presence of hallucinations (OR=6.12, CI=2.04-18.39) and delusions (OR=7.14, CI=2.23-22.93). Multiple linear regressions revealed that severity of anxiety remained an independent predictor (p<.05) of both the number of types of hallucinations (t=3.06, p=.003) and delusions (t=2.87, p=.005). Severity of depression was a significant predictor of the total number of delusions (t=2.28, p=.024). CONCLUSIONS: This study demonstrates an association between depression and psychosis and, for the first time, an association between anxiety and psychosis. These associations may have implications on pathophysiology and treatment of psychosis in PD.
Background: Disproportionate anterocollis is a debilitating condition which occurs in the later stages of parkinsonian syndromes and for which there is no effective therapy. Multiple hypotheses have been proposed to explain its underlying etiology, including myopathy of the cervical extensors, and dystonia of the cervical flexors.
Methods: We examined the records of 39 patients (8 prospectively) with anterocollis and parkinsonian syndromes to explore demographics, historical and clinical data, findings from electromyography and response to therapies. We classified our patients based on whether or not they were weak on neck extension and also based on primary diagnosis (PD vs atypical parkinsonian syndrome). Demographic, clinical, historical and EMG features are reported for each group.
Results: There were no significant demographic differences between clinical subtypes, or primary diagnosis. Electromyographic (EMG) findings demonstrated myopathic changes in both groups, although they were more prominent in the group which was weak in extension. Historical features were similar between groups except for dopamine agonist use, which was more common in the myopathic subgroup (p = 0.02). There were no other significant clinical differences between clinical subtypes or primary diagnosis with the exception that patients with atypical parkinsonian syndromes had more advanced motor symptoms. Conclusions: We conclude that anterocollis is a heterogeneous condition in which at least two distinct subtypes exist. Recognizing these subtypes may help guide therapy and future research.