Vanessa Fleury

Subthalamic stimulation may inhibit the beneficial effects of levodopa on akinesia and gait

Gait and akinesia deterioration in PD patients during the immediate postoperative period of DBS has been directly related to stimulation in the subthalamic region. The underlying mechanisms remain poorly understood. The aim of the present study was to clinically and anatomically describe this side effect.

Levodopa does not change cerebral vasoreactivity in Parkinson's disease

The aim of this work was to study cerebral vasoreactivity to hypercapnia in Parkinsons disease (PD) before and after levodopa administration. The prospective study was conducted in 20 patients presenting with PD, using 3T blood oxygenation level‐dependent (BOLD) functional MRI (fMRI) covering the whole brain. The hypercapnic stimulus was block‐designed using carbogen inhalation, a gas mixture of 7% CO2 and 93% O2, before (OFF) and 60 minutes after administration of a suprathreshold (120%) therapeutic L‐dopa dose (ON). Ten age‐matched controls were enrolled for between‐group comparisons. Analyses were conducted with a random effects model and corrected for multiple comparisons. No adverse reaction to the hypercapnic stimulus was reported. However, 10 patients and 2 controls were excluded because of incomplete protocol realization, inappropriate hypercapnic stimulus, or excessive movements, leaving 10 patients and 8 controls for further analyses. The hypercapnic stimulus increased whole‐brain BOLD signal of 1.48% ± 0.06% (mean ± standard error) in controls, 1.59% ± 0.05% in patients OFF, and 1.62% ± 0.09% in patients ON. Regions of interest analyses showed a signal increase in gray matter of 2.60% ± 0.16% in controls, 2.89% ± 0.21% in patients OFF, and 2.87% ± 0.12% in patients ON. No global or regional significant difference was detected, when comparing patients OFF and ON L‐dopa, or between patients and controls. Contrary to Alzheimers disease, the vasoreactivity to hypercapnia was normal in PD before and after L‐dopa administration, compared to controls. This negative result is an important finding, especially for neuroscientists using fMRI to investigate motricity and cognition, discarding a significant confounding effect.

Dopaminergic modulation of emotional conflict in Parkinson's disease

Neuropsychiatric fluctuations in Parkinsons disease (PD) are frequent and disabling. One way to investigate them is to assess the ability to inhibit distractive emotional information by a modified emotional Stroop (ES) task. We compared non-depressed, non-demented PD patients with healthy controls. During an acute levodopa challenge, patients performed a modified ES task during functional MRI and a neuropsychological assessment including Visual Analog Mood (VAMS) and Apathy scales. Ten patients and 12 controls completed the study. The VAMS scores were significantly improved by the acute intake of levodopa (p = 0.02), as was the apathy score (p = 0.03). Negative ES task (i.e. fearful facial expressions with the words “happy” or “fear” written across them), induced a lengthening of the mean reaction time during the incongruent trials compared with the congruent trials in controls (relative difference = 2.7%, p < 0.001) and in ON patients (relative difference = 5.9%, p < 0.001), but not in OFF patients (relative difference = 1.7%, p = 0.28). Controls and ON patients displayed greater activation than OFF patients within the right pregenual anterior cingulate cortex (pACC), an area specifically involved in emotional conflict resolution (p < 0.001 and p < 0.008 respectively, k > 5 uncorrected). No difference in the activation of the pACC was found between controls and ON patients, suggesting a normalization of the activation following levodopa administration. These results suggest that emotional conflict processes could be dopamine-dependent. Pregenual ACC hypoactivation could be directly due to the degeneration of dopaminergic mesocorticolimbic pathway. Our results propose that neuropsychiatric fluctuations in PD patients could be partially explained by pACC hypoactivation and that adjustments of dopaminergic medication might be helpful for their treatment.

Topiramate-induced delusional parasitosis

A 48-year-old woman with temporal lobe epilepsy and no prior history of psychiatric illness was started on topiramate (TPM). The dose was titrated up to 150 mg twice daily over 14 weeks and led to a significant reduction in seizure frequency. Upon reaching this dose, she developed intense pruritus and the firm belief that her skin was infected by parasites. She was diagnosed with delusional parasitosis (DP). Consequently, her TPM was weaned off and her DP settled completely without the use of antipsychotic medication. DP is characterized by the unshakeable conviction that small organisms infest the body despite the absence of confirmatory medical evidence. DP can occur in a wide variety of organic and psychiatric disorders or as an isolated delusional disorder. Rarely DP can be drug-induced. While psychiatric symptoms are a well recognized side-effect of TPM, this is, to our knowledge, the first reported case of TPM-induced DP.

Cardio-embolic cerebellar stroke secondary to mitral valve chordae rupture as a delayed complication of a high-voltage electrical injury

A 41-year-old farmer sustained a high-voltage electrical injury resulting in confusion, electrical burns and paroxysmal atrial fibrillation which spontaneously reverted to sinus rhythm after a few hours. Two weeks later he presented with a sudden onset of headache, unsteadiness, horizontal oscillopsia and paraesthesia in the right side of his face. Examination revealed nystagmus to the right, right-sided limb ataxia and a tendency to veer toward the right when walking. An MRI of the brain demonstrated an acute infarct of the right cerebellar hemisphere in the territory of the right posterior inferior cerebellar artery. A transesophageal echocardiogram showed a ruptured mitral valve chordae. This is the first report of a cardio-embolic stroke secondary to mitral valve chordae rupture as a delayed complication of high-voltage electrical injury. Although many mechanisms of direct cerebral electrical injury have been speculated, a cardio-embolic origin should not be overlooked as a cause of stroke secondary to high-voltage electrical injury.

Vertical supranuclear gaze palsy induced by deep brain stimulation: Report of two cases

Vertical supranuclear gaze palsy (VSGP) is etiologically diverse and can occur in a variety of neurological disorders, including stroke in acute onset cases, whereas a progressive onset is mainly encountered in neurodegenerative conditions such as progressive supranuclear palsy, or metabolic conditions such as NiemannePick type C disease [1]. Iatrogenic VSGP is exceptional and to date only one case of VSGP due to a small hemorrhage at the tip of one electrode was reported after implantation of deep brain stimulation (DBS) for Tourette syndrome [2]. Here we describe two patients who experienced reversible VSGP as a result of stimulation by misplaced DBS electrodes. Both patients gave their informed written consent for publication of their cases and videos. Patient 1 was a 51-year-old man who developed Parkinsons disease (PD) at the age of 42. After 6 years of dopaminergic treatment, he developed increasingly severe motor fluctuations and levodopa-induced dyskinesias, and as a result he underwent bilateral subthalamic nucleus (STN) DBS. Patient 2 was a 67-year-old male presenting with a 15 year history of essential tremor. Pharmacological treatment with propranolol, primidone, topiramate and gabapentin remained unsatisfactory. The patient was therefore evaluated for ventral intermediate nucleus of the thalamus (VIM) DBS. Under local anesthesia, quadripolar DBS electrodes (Model 3389, Medtronic, Minneapolis, MN; Kinetra, with contacts 0e3 for the right electrode and 4e7 for the left, with 0 and 4 being the most distal for patient 1; Activa PC, with contacts 0e3 for the right electrode and 8e11 for the left, with 0 and 8 being the most distal for patient 2) were implanted as previously described [3]. On the basis of the initial DBS programming performed a few days following surgery, DBS was switched on. A second DBS programming was performed, three months after surgery for patient 1 and six months after surgery for patient 2. Each contact was studied in a monopolar configuration with DBS parameters of 60 ms pulse width and 130 Hz frequency. During this programming, VSGP was induced by DBS. In patient 1, when the left STN-DBS was turned off and the right STN-DBS was turned on (contact 2e2.7 V/60 ms/130 Hz), horizontal and vertical ocular smooth pursuit and saccades were normal. When the left STN-DBS was turned on (contact 6-) while the right STN-DBS was still turned on, tor disturbances appeared from 2.3 V and were obvious supplementary video). The vertical ocular smooth pursuit and saccades were impossible downwards and severely altered upwards. The horizontal smooth pursuit and saccades were normal. Vertical and horizontal vestibulo-ocular reflexes (VOR) were normal with full vertical gaze movements. In patient 2, from 3.0 V on the left contact 8, an upward VSGP appeared while the right VIM-DBS was turned off. From 3.0 V on the right contact 0, a VSGP appeared. In both patients, VSGP resolved when the DBS was turned off (supplementary video) and was not experienced during testing of the other contacts. Supplementary data related to this article can be found online at http://dx.doi.org/10.1016/j.parkreldis.2014.07.007.

Short pulse width in subthalamic stimulation in Parkinson's disease: a randomized, double-blind study: Short Pulse Width in DBS

Background: We investigated the acute effect of short pulse widths on the therapeutic window in subthalamic nucleus deep brain stimulation in Parkinsons disease.

Localization of Deep Brain Stimulation Contacts Using Corticospinal/Corticobulbar Tracts Stimulation

Background Successful deep brain stimulation (DBS) in Parkinson’s disease (PD) requires optimal electrode placement. One technique of intraoperative electrode testing is determination of stimulation thresholds inducing corticospinal/corticobulbar tracts (CSBT) motor contractions. Objective This study aims to analyze correlations between DBS electrode distance to CSBT and contraction thresholds, with either visual or electromyography (EMG) detection, to establish an intraoperative tool devoted to ensure safe distance of the electrode to the CSBT. Methods Twelve PD patients with subthalamic nucleus DBS participated. Thresholds of muscular contractions were assessed clinically and with EMG, for three different sets of stimulation parameters, all monopolar: 130 Hz high-frequency stimulation (HFS); 2 Hz low-frequency stimulation with either 60 or 210 µs (LFS-60, LFS-210). The anatomical distance of electrode contacts to CSBT was measured from fused CT-MRI. Results The best linear correlation was found for thresholds of visually detected contractions with HFS (r2 = 0.63, p < 0.0001) when estimated stimulation currents rather than voltages were used. This correlation was found in agreement with an accepted model of electrical spatial extent of activation (r2 = 0.50). When using LFS, the correlation found remained lower than for HFS but increased when EMG was used. Indeed, the detection of contraction thresholds with EMG versus visual inspection did allow more frequent detection of face contractions, contributing to improve that correlation. Conclusion The correlation between electrode distance to the CSBT and contraction thresholds was found better when estimated with currents rather than voltage, eliminating the variance due to electrode impedance. Using LFS did not improve the precision of that evaluation, but EMG did. This technique provides a prediction band to ensure minimum distance of the electrode contacts to the CSBT, integrating the variance that can be encountered between prediction of models and practice.

Hyperdopaminergic behavioral spectrum in Parkinson's disease: A review

Impulse control disorders (ICDs) and other related behaviors, such as punding and dopamine dysregulation syndrome, are frequent yet underrecognized non-motor complications of dopamine replacement therapy (DRT) in Parkinsons disease (PD); they can also have a major negative impact on quality of life. They result from complex interactions between a given individuals predispositions, non-physiological dopaminergic stimulation and PD pathology. Also, sensitization of the mesocorticolimbic pathway, reflected by the psychotropic effects of dopaminergic treatment, plays a crucial role in the emergence of these addictive behaviors. While early detection of changes in behavior, less use of dopamine agonists (DA) that have a relative selectivity for mesocorticolimbic dopamine receptors, and fractionation of levodopa dosages to avoid non-physiological pulsatile stimulation of dopamine receptors are key strategies in the management of this hyperdopaminergic behavioral spectrum, other complementary approaches are also addressed in this review.

Prevalence of functional (psychogenic) parkinsonism in two Swiss movement disorders clinics and review of the literature

BACKGROUND Functional parkinsonism (FP) is considered rare but no studies have looked at its frequency. Case series have described high rates of comorbidity with Parkinsons disease (PD), suggesting a possible association between these conditions. OBJECTIVES To study the prevalence, epidemiology and clinical features of FP and its association with PD. METHODS We conducted a cross-sectional population-based prevalence study as well as a chart review of cases who received a diagnosis of FP over a 10-year-period in two movement disorder clinics in Switzerland. Epidemiological data regarding FP features were collected. The co-occurrence of PD, psychiatric disorders and other functional disorders were recorded. Clinical differences between FP and FP+PD groups are presented and discussed in light of a literature review. RESULTS The crude prevalence of FP was 0.64 per 100,000 in our population. FP represented 0.24% of patients with parkinsonism. Among 12 FP cases, female gender predominance (87%), mean age of onset of 45.5(±13.3 Standard deviation SD) years and prolonged diagnostic delay (mean 59±75 SD months) was found. Six patients had an additional diagnosis of PD, 83% of depression and 66% of other functional neurological disorder. In four patients with FP+PD, FP preceded PD by 6 to 56months. CONCLUSIONS These results suggest that FP should be considered in the differential diagnosis of patients presenting with parkinsonism. The high rate of co-occurrence with PD emphasizes the importance of long-term follow up of these patients. The observation that FP often precedes PD should be verified in prospective studies.