Thomas D. Hälbig

Subthalamic deep brain stimulation and impulse control in Parkinson’s disease

Background and purpose:  Experimental studies suggest that deep brain stimulation (DBS) of the subthalamic nucleus (STN) induces impulsivity in patients with Parkinson’s disease (PD). The purpose of this study was to assess various measures of impulse control in PD patients with STN DBS in comparison to patients receiving medical therapy.

Effects of levodopa on cognitive functioning in moderate-to-severe Parkinson’s disease (MSPD)

Summary.Although improved cognition has been reported in patients with mild Parkinson’s disease (PD) following the administration of levodopa, mixed results have been found in moderately-to-severely affected PD patients (MSPD), particularly in studies conducted since 1980. In the present study, 16 MSPD patients were tested on separate days, once following overnight levodopa withdrawal and once while optimally treated. A battery of neuropsychological tests that assess a range of cognitive functions (i.e., attention, language, visuospatial, memory, and executive), as well as a measure of depression, were used. Although patients performed better on a measure of confrontation naming in the untreated than in the treated condition, there were no significant differences for any of the other cognitive variables or for the depression scale variable. Thus, these data suggest that there are generally no adverse or beneficial effects of levodopa therapy on cognition in MSPD patients.

The Pattern of Cognitive-Functional Decline in Elderly Essential Tremor Patients: An Exploratory-Comparative Study With Parkinson's and Alzheimer's Disease Patients

OBJECTIVE Essential tremor (ET) is a neurological disorder that produces motor, cognitive, and functional disability. However, there has been no investigation linking cognitive impairment with functional disability in ET. Therefore, we examine the similarities and differences between ET, Alzheimers disease (AD), and Parkinsons disease (PD) in terms of the linkage between cognitive and functional impairment. DESIGN Thirty-four ET, 26 PD, and 31 AD subjects were tested for cognition (Mini-Mental State Examination [MMSE]), motor disability (United Parkinsons Disease Rating Scale part III [UPDRS-III]), and functional disability (Minimum Data Set-Activities of Daily Living Section [MDS-ADL]). RESULTS As expected, in PD and AD subjects, MDS-ADL scores significantly correlated with UPDRS-III and MMSE scores. The ET subjects showed a different pattern of functional disability with MDS-ADL scores significantly correlating only with MMSE scores, and with the orientation MMSE modalities. CONCLUSIONS Our findings highlight the need to be more cognizant of the nonmotor aspects of ET, which in some patients may be more functionally disabling than the motor features themselves.

The Effects of Withdrawal of Dopaminergic Medication in Nursing Home Patients With Advanced Parkinsonism

OBJECTIVE To determine the effects of dopaminergic medication withdrawal in an elderly, demented and minimally ambulatory nursing home population with parkinsonism in New York City. METHODS In our double-blind, randomized study, 11 patients (7 males, 4 females) were randomized into 2 groups: one group underwent levodopa medication withdrawal (experimental group) and the other group continued on their levodopa (control group). Patients were evaluated weekly over the course of a month with a neurologic examination and a series of assessment tools, including the motor UPDRS (Unified Parkinsons disease rating scale), Hoehn and Yahr staging scale, the Mini-Mental State Examination (MMSE) and the Nursing Assistant Behavioral Detection Form. SETTING An academic nursing home in New York City. RESULTS The patients had a mean age of 82.00 +/- 10.14 years, with a mean MMSE score of 9.50 +/- 6.60 out of 30.00 maximum. The control and experimental groups did not differ significantly with respect to age (P = .52), dementia severity (P = .35), nor severity of PD symptoms as measured by the UPDRS (P = .22) and Hoehn and Yahr staging (P = .65). Overall, no significant changes were observed between the control and experimental groups in cognitive, behavioral, and motor function across each time period. Of interest, 2 of the drug withdrawal patients showed modest improvements in cognitive function as measured by the MMSE. CONCLUSION Our findings suggest that in patients with advanced parkinsonism and dementia, dopaminergic medication withdrawal may be a feasible way to reduce polypharmacy and potential medication-related side effects, with a minimal risk of worsening motor deterioration. Therefore, our findings may have potential implications for a medication intervention that could prevent potential deleterious side effects and improve health-related quality of life in this frail population.

Differential role of dopamine in emotional attention and memory: Evidence from Parkinson's disease

Consistent with the hypothesis that dopamine is implicated in the processing of salient stimuli relevant to the modification of various behavioral responses, Parkinsons disease is associated with emotional blunting. To address the hypothesis that emotional attention and memory are modulated by dopaminergic neurotransmission in Parkinsons disease, we assessed 15 nondemented patients with Parkinsons disease while on and off dopaminergic medication and 15 age‐matched healthy controls. Visual stimuli were presented, and recognition was used to assess emotional memory. Response latency was used as a measure of emotional attention modulation. Stimuli were varied based on valence (pleasant, neutral, and unpleasant) and arousal (high and low) dimensions. Controls had significantly better memory for positive than negative stimuli, whereas patients with Parkinsons disease tested off medication had significantly better memory for negative than positive items. This negativity bias was lost when they were tested while on dopaminergic medication. Reaction times in patients with Parkinsons disease off medication were longer than in healthy controls and, paradoxically, were even longer when on medication. Further, although both healthy controls and patients with Parkinsons disease in the “off” state had arousal‐induced prolongation of reaction time, this effect was not seen in patients with Parkinsons disease on medication. These data indicate that dopaminergic neurotransmission is implicated in emotional memory and attention and suggest that dopamine mediates emotional memory via the valence dimension and emotional attention via arousal. Furthermore, our findings suggest that emotional changes in Parkinsons disease result from the effects of both the disease process and dopaminergic treatment.

Emotional processing affects movement speed.

Emotions can affect various aspects of human behavior. The impact of emotions on behavior is traditionally thought to occur at central, cognitive and motor preparation stages. Using EMG to measure the effects of emotion on movement, we found that emotional stimuli differing in valence and arousal elicited highly specific effects on peripheral movement time. This result has conceptual implications for the emotion–motion link and potentially practical implications for neurorehabilitation and professional environments where fast motor reactions are critical.

Skin picking in Parkinson's disease: A behavioral side‐effect of dopaminergic treatment?

IMPULSE CONTROL DISORDERS (ICD) as well as repetitive compulsive behaviors are increasingly being recognized in patients with Parkinson’s disease (PD), and have been attributed to the use of dopaminergic medications, and in particular to the use of dopamine agonists. Skin picking (SP) is a self-injurious, repetitive behavior that can cause significant tissue damage. It is included as an example of a potential ICD not otherwise specified in the DSM-IV-TR. SP has also been categorized as a stereotypical movement disorder, in that it is a disorder that is ‘repetitive, driven and nonfunctional’. Patients with SP often have important psychiatric comorbidity. Here we report a case of a PD patient who developed SP while being treated with levodopa and a dopamine agonist. The behavior was noted to resolve upon discontinuation of the dopamine agonist. A 51-year-old man had a 10-year history of PD. His initial symptoms consisted of a left hand tremor at rest and left-sided rigidity. In February 2008, the patient was brought to the clinic by his wife who complained that her husband had recently been ‘picking’ at his head. The skin picking had started a few weeks prior to the visit. There was no history of hair pulling behavior or of dermatological disease. In addition to levodopa 500 mg/day, entacapone 1000 mg/day and ropinirole 3 mg/ day, the patient took medications for chronic lower back pain (metaxalone, fentanyl patch, hydromorphone), and had also been treated since 2003 with paroxetine and lorazepam for mild depression and anxiety. The ropinirole had been added to the patient’s levodopa regimen in April 2006 to treat wearingoff symptoms related to the patient’s PD. The patient’s ropinirole dosage had been increased one month before the visit from 2 mg per day to 3 mg per day. Examination revealed the presence of five erythematous excoriated lesions of a diameter of 4 mm and depth of 2 mm on the patient’s frontal scalp. He denied any itching or tactile or visual hallucinations involving the scalp area. Neurological examination revealed findings consistent with the diagnosis of idiopathic PD. In the ‘ON’ state, the patient scored 14/108 on the motor part of the Unified Parkinson’s Disease Rating Scale. He was mildly dyskinetic, had pressured speech and hyperactive behavior. The patient was tapered off ropinirole while the remainder of his medication regimen remained unchanged. After having been off ropinirole for two months, the patient and his wife reported that he had stopped picking at his scalp. His hypomanic behavior had also resolved. Formal neuropsychological testing revealed a mild subcortical dementia as well as mild depression and anxiety. While ICDs such as pathological gambling or compulsive shopping have been described as side-effects of dopaminergic treatment in PD, to the best of our knowledge SP has not previously been reported in PD. Although the patient was on other psychoactive medications that may have contributed, the fact that the SP resolved upon discontinuation of his dopamine agonist supports the hypothesis that this behavior could represent a behavioral side-effect of dopaminergic medication similar to other ICDs. ICDs in PD may be induced in predisposed patients by dopaminergic treatment, and in particular dopamine agonists, probably via excessive stimulation or sensitization of dopamine receptors in mesolimbic structures. In conclusion, we report a PD patient who developed a new onset SP, in the context of dopamine agonist therapy. Given the potential self-injurious nature of this behavior, physicians should monitor patients for the development of this possible behavioral complication of dopaminergic therapy.

Effects of dopaminergic and subthalamic stimulation on musical performance

Although subthalamic-deep brain stimulation (STN-DBS) is an efficient treatment for Parkinson’s disease (PD), its effects on fine motor functions are not clear. We present the case of a professional violinist with PD treated with STN-DBS. DBS improved musical articulation, intonation and emotional expression and worsened timing relative to a timekeeper (metronome). The same effects were found for dopaminergic treatment. These results suggest that STN-DBS, mimicking the effects of dopaminergic stimulation, improves fine-tuned motor behaviour whilst impairing timing precision.

Preserved Emotional Modulation of Motor Response Time Despite Psychomotor Slowing in Young-Old Adults

ABSTRACT Whereas aging affects cognitive and psychomotor processes negatively, the impact of aging on emotional processing is less clear. Using an “old–new” binary decision task, we ascertained the modulation of response latencies after presentation of neutral and emotional pictures in “young” (M = 27.1 years) and “young-old” adults with a mean age below 60 (M = 57.7 years). Stimuli varied on valence (pleasant, neutral, and unpleasant) and arousal (high and low) dimensions. Young-old adults had significantly longer reaction times. However, young and young-old adults showed the exact same pattern of response time modulation by emotional stimuli: Response latencies were longer for high-arousal than for low-arousal pictures and longer for negative than for positive or neutral stimuli. This result suggests that the specific effects of implicitly processed emotional valence and arousal information on behavioral response time are preserved in young-old adults despite significant age-related psychomotor decline.