Neepa Patel

Sensory aspects of movement disorders

Movement disorders, which include disorders such as Parkinsons disease, dystonia, Tourettes syndrome, restless legs syndrome, and akathisia, have traditionally been considered to be disorders of impaired motor control resulting predominantly from dysfunction of the basal ganglia. This notion has been revised largely because of increasing recognition of associated behavioural, psychiatric, autonomic, and other non-motor symptoms. The sensory aspects of movement disorders include intrinsic sensory abnormalities and the effects of external sensory input on the underlying motor abnormality. The basal ganglia, cerebellum, thalamus, and their connections, coupled with altered sensory input, seem to play a key part in abnormal sensorimotor integration. However, more investigation into the phenomenology and physiological basis of sensory abnormalities, and about the role of the basal ganglia, cerebellum, and related structures in somatosensory processing, and its effect on motor control, is needed.

Alleviating manoeuvres (sensory tricks) in cervical dystonia

Background There is limited information on the phenomenology, clinical characteristics and pathophysiology of alleviating manoeuvres (AM), also called ‘sensory tricks’ in cervical dystonia (CD). Methods Individual data, collected from 10 sites participating in the Dystonia Coalition (http://clinicaltrials.gov/show/NCT01373424), included description of localisation and phenomenology of AM collected by systematic review of standardised video examinations. Analyses correlated demographic, neurologic, and psychiatric features of CD patients with or without effective AM. Results Of 154 people studied, 138 (89.6%) used AM, of which 60 (43.4%) reported partial improvement, 55 (39.8%) marked improvement, and 4 (0.03%) no effect on dystonic posture. Light touch, usually to the lower face or neck, was used by >90%. The presence or location of AM did not correlate with the severity of the dystonia. Conclusions In this large and comprehensive study of CD, we found no clinical predictors of effective AM. Further studies of sensorimotor integration in dystonia are needed to better understand the pathophysiology of AM.

Habituation and rebound to thalamic deep brain stimulation in long-term management of tremor associated with demyelinating neuropathy

Some patients may experience tolerance to chronic ventral intermediate (ViM) thalamic deep brain stimulation (DBS), which may include habituation (loss of sustained tremor control over weeks to days after an adjustment) and rebound (a temporary increase in tremor intensity after stopping DBS). We observed an association between these efficacy limiting phenomena with co-morbid demyelinating sensorimotor peripheral neuropathy (MRT-PN). The clinical and treatment characteristics of neuropathy and tremor pre- and post-DBS are described through retrospective chart review of five patients with MRT-PN. Programming strategies (number of programming visits/implant years and number of major parameter changes/electrode) were compared in MRT-PN patients to a group of seven ET patients without neuropathy, who had >4 years continuous follow-up. The presence of habituation and rebound were recorded. All MRT-PN patients had initial good response to DBS followed by habituation and/or rebound of tremor control, some asymmetrically. Compared to ET without neuropathy (mean follow-up 5.83 ± 0.78 years), MRT-PN patients (mean follow-up 4.90 ± 3.73years) required more programming visits/year (p = 0.12) and major parameter changes/electrode/implant year (p = 0.03). The presence of neuropathy may alter tremor characteristics and result in temporary re-setting of thalamic oscillatory drive after DBS in MRT-PN patients. Clinicians should be aware of the risk for tolerance to DBS in MRT-PN and patients should be counseled about possible suboptimal sustained tremor control.

Psychosis in Parkinson Disease: A Review of Etiology, Phenomenology, and Management.

Parkinson disease psychosis (PDP) is a common phenomenon in Parkinson disease (PD) patients treated with dopaminergic drugs, and is associated with high morbidity and mortality. It also correlates with depression and dementia, and can contribute to considerable caregiver stress and burnout. While symptoms can be relieved by decreasing doses or number of anti-PD medications, this may lead to an unacceptable worsening of motor function. When general medical or psychiatric conditions have been ruled out, and decreasing dopaminergic agents is not effective in treating psychosis, therapies include atypical antipsychotics, primarily clozapine and quetiapine. Of these, clozapine is effective but is associated with a poor side-effect profile and the necessity for frequent blood draws. Clinicians prefer quetiapine for its theoretically better safety profile, although there is no evidence for efficacy in treating psychosis. All atypical antipsychotics are associated with increased mortality in this patient population. Cholinesterase inhibitors can ameliorate psychosis symptoms. The serotonin 5-HT2A receptor inverse agonist pimavanserin was recently approved by the US FDA for the treatment of PDP and may prove to be a more targeted therapy without the downsides of atypical antipsychotics.

Developing a Deep Brain Stimulation Neuromodulation Network for Parkinson Disease, Essential Tremor, and Dystonia: Report of a Quality Improvement Project.

Objective To develop a process to improve patient outcomes from deep brain stimulation (DBS) surgery for Parkinson disease (PD), essential tremor (ET), and dystonia. Methods We employed standard quality improvement methodology using the Plan-Do-Study-Act process to improve patient selection, surgical DBS lead implantation, postoperative programming, and ongoing assessment of patient outcomes. Results The result of this quality improvement process was the development of a neuromodulation network. The key aspect of this program is rigorous patient assessment of both motor and non-motor outcomes tracked longitudinally using a REDCap database. We describe how this information is used to identify problems and to initiate Plan-Do-Study-Act cycles to address them. Preliminary outcomes data is presented for the cohort of PD and ET patients who have received surgery since the creation of the neuromodulation network. Conclusions Careful outcomes tracking is essential to ensure quality in a complex therapeutic endeavor like DBS surgery for movement disorders. The REDCap database system is well suited to store outcomes data for the purpose of ongoing quality assurance monitoring.

Pseudobulbar Affect Correlates With Mood Symptoms in Parkinsonian Disorders but Not Amyotrophic Lateral Sclerosis

Pseudobulbar affect (PBA) is a syndrome of affective disturbance associated with inappropriate laughter and crying, independent of mood. PBA is common in amyotrophic lateral sclerosis (ALS) and increasingly recognized in Parkinsons disease (PD) and atypical parkinsonism (aP). Correlates of PBA have not been systematically studied. The purpose of this study was to determine whether cognitive and psychiatric comorbidities correlated with patient-reported symptoms of PBA by using the Center for Neurological Study-Lability Scale among patients with ALS, PD, and aP. A total of 108 patients (PD, N=53; aP, N=29; ALS, N=26) completed a cognitive screener and self-reported measures of lability, depression, anxiety, apathy, and quality of life. Statistical analyses included one- and two-way analyses of covariance to evaluate group differences, Pearsons correlations to determine relationships between PBA symptoms and comorbidities, multiple regression for predicting PBA symptom severity in clinical correlates, and chi-square t tests for predicting demographic variables. PBA symptom severity did not vary between the three groups. Younger age and worse anxiety correlated with PBA symptom severity in all three groups, whereas depression and poor mental health/quality of life only correlated with PBA symptom severity in the PD and aP groups. PD and aP patients may be more likely to benefit from treatment with antidepressants. Increased PBA symptoms were associated with declines in cognitive functioning in the aP group, but sufficient numbers of PD and ALS patients with cognitive dysfunction may not have been recruited. The results suggest the possibility of an alternate pathophysiologic mechanism for PBA, which may vary between neurological disorders and disease progression. Mood and cognition are of particular relevance and should be evaluated when symptoms of PBA are suspected.

Cervical dystonia and substance abuse

ObjectiveTo investigate the prevalence of substance abuse (SA) in patients with cervical dystonia (CD) and to correlate it with prevalence of psychiatric disorders.MethodsData on anxiety, depression, dystonia severity, and substance abuse were collected from ten sites participating in the Dystonia Coalition. Patients were divided into two groups according to the presence of SA, utilizing Structured Clinical Interview for DSM-4 criteria. Wilcoxon Rank-Sum test was used to analyze the difference in median scores on the questionnaires between the groups. Chi-square test was used to analyze association between opiate and benzodiazepine use and SA. Association between TWSTRS severity and SA and medication use was assessed. A two-tailed p value of < 0.05 was considered significant. SAS 9.3 (SAS Institute Inc., Cary, NC, USA) was used for all analyses.ResultsOf 208 CD patients, 23 (11%) were identified with SA; 26.3% of patients with SA were on opiates compared to 7.2% of CD patients without SA (p = 0.006). Compared to non-SA patients, those experiencing SA were more likely male (88.9%; p = 0.0007), younger (median age 55; p = 0.031), and scored worse on questionnaires assessing depression (p = 0.044, p = 0.005), anxiety (p = 0.003), and dystonia psychiatric severity (p = 0.033). The median TWSTRS motor severity scores were higher in SA patients compared to non-SA patients (20 versus 16, p = 0.0339). The median TWSTRS total disability, motor, and pain scores were higher in patients on opiates than patients who were not (12 versus 8, p = 0.0071; 18.5 versus 16, p = 0.0243; 12.4 versus 6.7, p = 0.0052, respectively).ConclusionsPotential risk factors for SA in CD patients include younger age and male gender with comorbid anxiety, depression and other psychiatric problems. Caution should be exercised when prescribing drugs with potential for abuse in these patients.

Cervical Dystonia and Executive Function: A Pilot Magnetoencephalography Study

Background: Cervical dystonia (CD) patients have impaired working memory, processing speed and visual-motor integration ability. We used magnetoencephalography (MEG) to investigate changes in cerebral oscillations in CD patients during an executive function test, before and after administration of botulinum toxin. Methods: MEG data were collected from five CD patients while they performed a visual continuous performance task (CPT), before and after they received a botulinum toxin injection. MEG data was also collected on five controls matched for age and gender. Coherence source imaging was performed to quantify network connectivity of subjects. Results: Controls demonstrated two errors with visual CPT; CD patients demonstrated six and three errors pre- and post-botulinum toxin respectively. After botulinum toxin, mean time from cue to correct response was 0.337 s in controls, 0.390 s in patients before botulinum toxin injection, and 0.366 s after the injection. Differences in coherence between controls and patients were found in the following brain regions: Fronto-frontal, fronto-parietal, fronto-striatal, fronto-occipital, parieto-parietal and temporo-parietal. Intrahemispheric and interhemispheric networks were affected. Post injection, there was minimal change in coherence in the above-mentioned networks. Discussion: Neuropsychological testing suggests difference in coherence in frontal circuits between CD cases and controls during the visual CPT, which may reflect subjects’ increased difficulty with the task. Botulinum toxin is associated with minimal improvement with executive function in CD.

Comparison of Globus Pallidus Interna and Subthalamic Nucleus in Deep Brain Stimulation for Parkinson Disease: An Institutional Experience and Review

Deep Brain Stimulation (DBS) has revolutionized the lives of patients of Parkinson disease, offering therapeutic options to those not benefiting entirely from medications alone. With its proven track record of outperforming the best medical management, the goal is to unlock the full potential of this therapy. Currently, the Globus Pallidus Interna (GPi) and Subthalamic Nucleus (STN) are both viable targets for DBS, and the choice of site should focus on the constellation of symptoms, both motor and nonmotor, which are key determinants to quality of life. Our article sheds light on the specific advantages and drawbacks of the two sites, highlighting the need for matching the inherent properties of a target with specific desired effects in patients. UT Southwestern Medical Center has a robust and constantly evolving DBS program and the narrative from our center provides invaluable insight into the practical realities of DBS. The ultimate decision in selecting a DBS target is complex, ideally made by a multidisciplinary team, tailored towards each patients profile and their expectations, by drawing upon scientific evidence coupled with experience. Ongoing research is expanding our knowledge base, which should be dynamically incorporated into an institutes DBS paradigm to ensure that patients receive the optimal therapy.

Tics and Tourette Syndrome: Phenomenology

Tourette syndrome (TS) is a common neurologic and behavioral disorder, primarily characterized by the presence of motor and phonic tics. Tics are defined as brief and involuntary movements or sounds, often preceded by a premonitory sensation or urge. Some motor tics may be quite complex and phonic tics may manifest as semantically meaningful utterances, including profanities and obscenities (coprolalia). The natural history of TS is a waxing and waning course with reduction in symptom severity in adulthood in majority of cases. Common behavioral comorbidities include obsessive-compulsive disorder, attention-deficit disorder, and impulse control disorder.