Gonzalo J. Revuelta

Clinical subtypes of anterocollis in parkinsonian syndromes

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.

Reward circuit DBS improves Parkinson's gait along with severe depression and OCD.

ABSTRACT A 59-year-old Caucasian man with a past history of Parkinson’s disease (PD) status post-bilateral subthalamic nucleus (STN) deep brain stimulation (DBS), who also had treatment-resistant (TR) obsessive–compulsive disorder (OCD), and treatment-resistant depression (TRD), presented for further evaluation and management of his TR OCD. After an unsuccessful attempt to treat his OCD by reprogramming his existing STN DBS, he was offered bilateral ventral capsule/ventral striatum (VC/VS) DBS surgery. In addition to the expected improvement in OCD symptoms, he experienced significant improvement in both PD-related apathy and depression along with resolution of suicidal ideation. Furthermore, the patient’s festinating gait dramatically improved. This case demonstrates that DBS of both the STN and VC/VS appears to have an initial signal of safety and tolerability. This is the first instance where both the STN and the VC/VS DBS targets have been implanted in an individual and the first case where a patient with PD has received additional DBS in mood-regulatory circuitry.

Forced Exercise for Freezing of Gait in Post STN DBS ParkinsonâÂÂs DiseasePatients

Freezing of gait (FoG) is a debilitating condition experienced by Parkinson’s disease (PD) patients whereby they are episodically unable to walk despite their intention to do so. Early, it may occur in the OFF state, and responds to dopaminergic therapy and deep brain stimulation (DBS). FoG can also occur in the ON state, termed non-levodopa responsive FoG (NLR-FoG). The objective of this study was to determine the effects of a forced exercise treadmill protocol on NLR-FoG in patients with PD that had undergone DBS. We recruited five patients to complete a progressive treadmill-training program for six weeks. The freezing of gait questionnaire (FoG-Q) was the primary outcome measure. Patients also completed diaries documenting the number of freezing episodes and falls, the gait and falls questionnaire (GFQ), as well as PD motor and balance assessments pre and post treatment. Objective assessment of spatiotemporal gait parameters were also collected pre and post treatment. We did not see a significant difference in the FoG-Q pre and post treatment. We did see improvements in the MDS-UPDRS in 4/5 patients, and improvements in falls and freezing as measured by diaries in 3/5 patients. Improvement in spatiotemporal gait parameters beyond the minimal detectible change was seen in 2/5 patients. In conclusion, we found that a progressive forced exercise protocol is feasible in patients with PD post DBS, but response to treatment was not uniform. Further larger studies to elucidate factors predictive of response in this patient population are warranted.

Collum-caput (COL-CAP) concept for conceptual anterocollis, anterocaput, and forward sagittal shift.

OBJECTIVES Anterocollis as a rare subtype of cervical dystonia is difficult to treat and thus less appreciated than other subtypes of cervical dystonia. This review aimed at summarising and discussing recent advances in the management of anterocollis. METHODS Literature review. RESULTS Pure anterocollis is a rare condition but 1-24% of the cases of complex cervical dystonia present with an anterocollis component. Applying the collum-caput concept, anterocollis may be subdivided into conceptual anterocollis, anterocaput, and forward sagittal shift, which is useful to direct selection of dystonic muscles for treatment. Additionally, identification of dystonic muscles in conceptual anterocollis, anterocaput, or forward sagittal shift is achieved by electromyography, computed tomography, magnetic resonance imaging, or FDG-positron emission tomography. Treatment of choice is botulinum toxin A. In case of treatment failure, more rarely affected muscles need to be identified and injected. Deep muscles, as are frequently involved in conceptual anterocollis, anterocaput, and forward sagittal shift, should be injected only under guidance of electromyography, endoscopy, or imaging. The more accurately affected muscles are identified, the better the outcome. CONCLUSIONS Anterocollis as a subtype of cervical dystonia, responds poorly to botulinum toxin but management of this condition can be improved by application of identifying and guiding technologies.

Unilateral ultra-brief pulse electroconvulsive therapy for depression in Parkinson's disease

Electroconvulsive therapy (ECT) has demonstrated efficacy in treating core symptoms of Parkinsons disease (PD); however, widespread use of ECT in PD has been limited due to concern over cognitive burden. We investigated the use of a newer ECT technology known to have fewer cognitive side effects (right unilateral [RUL] ultra‐brief pulse [UBP]) for the treatment of medically refractory psychiatric dysfunction in PD.

A Double-Blind, Sham-Controlled Pilot Trial of Pre-Supplementary Motor Area (Pre-SMA) 1 Hz rTMS to Treat Essential Tremor.

Please cite this article as: Bashar W. Badran, Chloe E. Glusman, Chris W. Austelle, Shonna Jenkins, William H. DeVries, Virginia Galbraith, Tiffani Thomas, Thomas G. Adams Jr, Mark S. George, Gonzalo J Revuelta, A Double-Blind, Sham-Controlled Pilot Trial of Pre-Supplementary Motor Area (Pre-SMA) 1Hz rTMS to Treat Essential Tremor, Brain Stimulation (2016), http://dx.doi.org/doi: 10.1016/j.brs.2016.08.003.

An 18F-FDG PET study of cervical muscle in parkinsonian anterocollis

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 (18)F-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 (18)F-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.

Anterocollis and Camptocormia in Parkinsonism: A Current Assessment

Postural deformities in parkinsonian syndromes are well recognized, but poorly understood and largely refractory to available therapies. In recent times a number of hypotheses have been proposed to explain the underlying etiology of anterocollis and camptocormia, but currently there is no consensus. As these conditions are more precisely characterized we begin to uncover that this is a heterogeneous and evolving phenomenon. These conditions bring to light the inadequacies of our current tools to study biomechanics of posture, neuromuscular disorders, and dystonic muscular contractions. The development of objective, accurate tools to directly study and measure the severity of these postural disorders will allow for further understanding of the pathophysiology, the development of novel therapeutics, and adequate clinical trial design.

The Role of Amantadine Withdrawal in 3 Cases of Treatment-refractory Altered Mental Status

Amantadine, which was originally developed as an antiviral medication, functions as a dopamine agonist in the central nervous system and consequently is utilized in the treatment of Parkinson disease, drug-induced extrapyramidal reactions, and neuroleptic malignant syndrome. For reasons that are not entirely understood, abrupt changes in amantadine dosage can produce a severe withdrawal syndrome. Existing medical literature describes case reports of amantadine withdrawal leading to delirium, which at times has progressed to neuroleptic malignant syndrome. Amantadine withdrawal may be under-recognized by mental health clinicians, which has the potential to lead to protracted hospital courses and suboptimal outcomes. The goal of this case series is to highlight the role of amantadine withdrawal in the cases of 3 medically complex patients with altered mental status. In the first case, the cognitive side effects of electroconvulsive therapy masked acute amantadine withdrawal in a 64-year-old man with Parkinson disease. In the second case, a 75-year-old depressed patient developed a catatonic delirium when amantadine was discontinued. Finally, a refractory case of neuroleptic malignant syndrome in a 57-year-old patient with schizoaffective disorder rapidly resolved with the reintroduction of outpatient amantadine. These cases highlight several learning objectives regarding amantadine withdrawal syndrome: First, it may be concealed by co-occurring causes of delirium in medically complex patients. Second, its symptoms are likely to be related to a cortical and limbic dopamine shortage, which may be reversed with electroconvulsive therapy or reintroduction of amantadine. Third, its clinical presentation may occur on a spectrum and may include features suggestive of delirium, catatonia, or neuroleptic malignant syndrome.

Pilot study of atomoxetine in patients with Parkinson’s disease and dopa-unresponsive Freezing of Gait

BackgroundFreezing of gait (FoG) is a common and debilitating condition in Parkinson’s disease (PD) associated with executive dysfunction. A subtype of FoG does not respond to dopaminergic therapy and may be related to noradrenergic deficiency. This pilot study explores the effects of atomoxetine on gait in PD patients with dopa-unresponsive FoG using a novel paradigm for objective gait assessment.FindingsTen patients with PD and dopa-unresponsive FoG were enrolled in this eight-week open label pilot study. Assessments included an exploratory gait analysis protocol that quantified spatiotemporal parameters during straight-away walking and turning, while performing a dual task. Clinical, and subjective assessments of gait, quality of life, and safety were also administered. The primary outcome was a validated subjective assessment for FoG (FOG-Q). Atomoxetine was well tolerated, however, no significant change was observed in the primary outcome. The gait analysis protocol correlated well with clinical scales, but not with subjective assessments. DBS patients were more likely to increase gait velocity (p = 0.033), and improved in other clinical assessments.ConclusionsObjective gait analysis protocols assessing gait while dual tasking are feasible and useful for this patient population, and may be superior correlates of FoG severity than subjective measures. These findings can inform future trials in this population.