Parkinson Disease: Okun MS

Okun MS, Fernandez HH. · No affiliation provided · Neurology. · Pubmed #19092111 No free full text.

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Kenney C, Fernandez HH, Okun MS. · No affiliation provided · Expert Rev Neurother. · Pubmed #17563240 No free full text.

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Okun MS, Foote KD. · No affiliation provided · Arch Neurol. · Pubmed #15824249 links to  free full text

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Hooper AK, Okun MS, Foote KD, Fernandez HH, Jacobson C, Zeilman P, Romrell J, Rodriguez RL. · University of Florida, Movement Disorders Center, Gainesville, FL 32601, USA. · Stereotact Funct Neurosurg. · Pubmed #18334856 No free full text.

Abstract: Deep brain stimulation (DBS) surgery has become the gold standard for treatment of select refractory cases of Parkinson disease and essential tremor. Despite the usefulness of DBS surgery in many cases, there remain situations where lesion therapy (subthalamotomy, pallidotomy or thalamotomy) may provide a reasonable alternative to DBS. We reviewed the University of Florida Institutional Review Board-approved database for movement disorders surgery and identified 286 DBS leads placed in 189 patients as well as 4 additional patients who had lesion therapy. In these 4 cases we reviewed the clinical presentations that resulted in a multidisciplinary team opting for lesion therapy over DBS. Lesion therapy represents a viable alternative and has several important advantages, including a decreased need for access to specialists and clinical follow-up, improved affordability, and a lower infection risk.

Rodriguez RL, Fernandez HH, Haq I, Okun MS. · Department of Neurology, University of Florida Movement Disorders Center, McKnight Brain Institute, Gainesville, Florida, USA. · Neurologist. · Pubmed #17848865 No free full text.

Abstract: BACKGROUND: Deep brain stimulation (DBS) has emerged as an important treatment for medication refractory movement and neuropsychiatric disorders. General neurologists and even general practitioners may be called upon to screen potential candidates for DBS. The patient selection process plays an important role in this procedure. REVIEW SUMMARY: In this article, we discuss "pearls" for the clinician who may be called upon to identify appropriate candidates for DBS. Additionally, we will discuss the important points that should be considered when referring patients for surgical intervention. CONCLUSION: Diagnosis, response to levodopa, cognitive status, psychiatric status, access to care, and patient expectations are all essential elements of the patient selection process for DBS. These areas must be adequately addressed prior to any surgical procedure.

Sudhyadhom A, Bova FJ, Foote KD, Rosado CA, Kirsch-Darrow L, Okun MS. · Department of Neurology, McKnight Brain Institute, 100 South Newell Drive, Gainesville, FL 32610, USA. · Curr Neurol Neurosci Rep. · Pubmed #17618533 No free full text.

Abstract: The use of deep brain stimulation (DBS) has recently been expanding for the treatment of many neurologic disorders such as Parkinson disease, dystonia, essential tremor, Tourette's syndrome, cluster headache, epilepsy, depression, and obsessive compulsive disorder. The target structures for DBS include specific segregated territories within limbic, associative, or motor regions of very small subnuclei. In this review, we summarize current clinical techniques for DBS, the cognitive/mood/motor outcomes, and the relevant neuroanatomy with respect to functional territories within specific brain targets. Future development of new techniques and technology that may include a more direct visualization of "motor" territories within target structures may prove useful for avoiding side effects that may result from stimulation of associative and limbic regions. Alternatively, newer procedures may choose and specifically target non-motor territories for chronic electrical stimulation.

Okun MS, Fernandez HH, Rodriguez RL, Foote KD. · Department of Neurology, University of Florida Movement Disorders Center, McKnight Brain Institute, Gainesville, USA. · Geriatrics. · Pubmed #17489644 No free full text.

Abstract: Deep brain stimulation (DBS) can improve symptoms in well-selected patients with Parkinson's disease. Primary care physicians must take into account many important issues when considering referral for DBS. The Florida Surgical Questionnaire for PD (FLASQ-PD), a 5-section screening tool that can help primary care providers identify appropriate DBS candidates, can be filled out and scored by a general practitioner, advanced clinical nurse practitioner, physician assistant, or trained nurse. Potential candidates who score well on this questionnaire can be referred for presurgical multidisciplinary evaluation at an experienced DBS implanting center.

Skidmore FM, Rodriguez RL, Fernandez HH, Goodman WK, Foote KD, Okun MS. · Department of Neurology, McKnight Brain Institute, University of Florida College of Medicine in Gainesville, 32610, USA. · CNS Spectr. · Pubmed #16816792 links to  free full text

Abstract: The introduction of deep brain stimulation (DBS) as a treatment for medication-refractory essential tremor in the late 1980s revealed, for the first time, that "chronically" implanted brain hardware had the potential to modulate neurologic function with surprisingly low morbidity. Over time, the therapeutic promise of DBS has become evident in Parkinson's disease and dystonia. In some experienced centers, complex tremor disorders, such as posttraumatic Holmes tremor and the tremor of multiple sclerosis, are being increasingly targeted. More recently, other indications, including obsessive-compulsive disorder, Tourette's syndrome, major depression, and chronic pain, have been proposed. As the field has expanded, our knowledge about potential cognitive side effects of DBS has also expanded. This article reviews the current knowledge regarding the impact of stimulation of the subthalamic nucleus, globus pallidus internus, and ventralis intermedius nucleus of the thalamus on symptoms in essential tremor, Parkinson's disease, and dystonia. Also discussed are the emerging targets, what is known about the cognitive sequelae of DBS, and what has been learned about the complications and therapeutic failures.

Bruce BB, Foote KD, Rosenbek J, Sapienza C, Romrell J, Crucian G, Okun MS. · Department of Neurology, McKnight Brain Institute, Movement Disorders Center, University of Florida, Gainesville, FL 32610, USA. · Stereotact Funct Neurosurg. · Pubmed #15557767 No free full text.

Abstract: Patients may present with classical symptoms suggesting aphasia following thalamotomy (repetition, comprehension, fluency and naming abnormalities). They may also present with 'freezing of speech', and this symptom should not be considered as a speech disorder or a symptom of Parkinson's disease progression, without careful testing to rule out language deficits, particularly dysfluency. There are important issues related to all language complications of thalamotomy, including (1) the time course of problems following surgery, (2) the impact of preexistingspeech problems, (3) the importance of the size and location of lesions, (4) the potential circuits important in the pathogenesis of a thalamic language disturbance and (5) whether laterality makes a difference (left- versus right-sided thalamic lesions). As more centers switch from thalamotomy to deep brain stimulation, the issues regarding aphasia will need to be addressed.

Wint DP, Okun MS, Fernandez HH. · Department of Psychiatry, McKnight Brain Institute/University of Florida, Gainesville 32610, USA. · J Geriatr Psychiatry Neurol. · Pubmed #15312276 No free full text.

Abstract: Psychosis in Parkinson's disease (PD) is a fairly common and vexing problem. Although it can occur at any stage of the illness, it is a particularly important issue for patients who are in the later stages of PD and have been chronically treated with anti-PD medications. The exact pathophysiology of PD-related psychosis remains a mystery. Neurochemical imbalances, sleep disturbances, and visual processing abnormalities in PD have been implicated in its pathogenesis. Treatment of psychotic symptoms should occur only after potential medical and environmental causes of delirium have been eliminated or addressed. Initial pharmacologic changes should include limiting the patient's anti-PD medications to those that are necessary to preserve motor function. Should that fail, an atypical antipsychotic agent is presently the treatment of choice. An emerging treatment option is the use of acetylcholinesterase inhibitors. This article reviews what is known about the epidemiology, risk factors, pathophysiology, and treatment of PD-related psychosis.

Okun MS, Vitek JL. · Department of Neurology, University of Florida, Gainesville, Florida, USA. · Mov Disord. · Pubmed #15077235 No free full text.

Abstract: An analysis of the international literature on lesioning for movement disorders was undertaken to review lesion therapy for Parkinson's disease (PD) and other movement disorders and to highlight important controversies surrounding this surgical technique. Lesions have been placed throughout the neuraxis with varying approaches and success. Our understanding of the pathophysiological basis underlying the development of PD and other movement disorders has led to a better understanding of why lesioning certain portions of the nervous system should improve motor function. Advances in imaging technology and electrophysiological techniques used for localization of brain structures, such as microelectrode mapping, have improved the ability to accurately identify and lesion target structures deep in the brain. This improvement has led to an increase in the degree and consistency of clinical benefit. The major controversies in lesion therapy include: (1) which target for which disorder; (2) determination of the optimal lesion site and whether the external globus pallidus (GPe) should be included in the pallidotomy lesion for PD; (3) determination of the size of the lesion; (4) whether bilateral lesions can be placed without the high incidence of side effects reported by some investigators; (5) whether microelectrodes aid in the ability to improve clinical outcomes or increase the risk of side effects by making multiple microelectrode penetrations; (6) whether the subthalamic nucleus (STN) should be explored further as a lesioning target; and (7) whether lesioning should be abandoned entirely in favor of deep brain stimulation (DBS). Many important questions and controversies regarding lesion therapy remain unanswered. It is unlikely given the pro-DBS environment that these questions will be answered in the near future. We should, however, be careful not to abandon an effective therapy before fully exploring through randomized trials the relative effect of different surgical approaches for the treatment of patients with movement disorders.

Romrell J, Fernandez HH, Okun MS. · University of Florida, Department of Neurology, McKnight Brain Institute, PO Box 100236, Gainesville, FL 32610, USA. · Expert Opin Pharmacother. · Pubmed #14521485 No free full text.

Abstract: Parkinson's disease (PD) is a neurodegenerative disorder that affects an estimated 1 million people in the US and tens of millions worldwide. Medication therapy has made significant advances and improvements especially over the last 10 years. A number of new treatments and new strategies have emerged and the quality of life for the average sufferer has improved. This review will describe the rationale and strategies for current medical therapies in PD, with special emphasis on the use of antipsychotic agents. Levodopa remains the most efficacious medication for the management of PD. Long-term use of levodopa, however, is associated with the development of motor fluctuations including dyskinesia. Trials with dopamine agonists have demonstrated a delay in the onset of dyskinesia with the use of this therapy. There is also active, ongoing investigation to determine whether a neuroprotective effect may be present with agonist therapy. Anticholinergics have been successfully used to treat tremor as well as sialorrhoea and urinary urgency. Catechol-O-methyltransferase inhibitors increase 'on time', decrease 'off time,' and improve motor scores. Continuous stimulation of dopamine receptors may decrease the fluctations observed with pulsatile delivery of anti-Parkinsonian medications, but this will require more study. Monoamine oxidase-B inhibitors, specifically selegiline, may provide symptomatic improvement; the question as to whether a neuroprotective benefit is present remains unanswered. Amantadine has demonstrated both symptomatic benefit and dyskinesia benefit in some patients. Selective dopamine blockers such as clozaril and quetiapine, have been shown to be effective in the treatment of psychosis. This class of medications is particularly useful as an adjunctive to levodopa and dopamine agonists. Doses of dopaminergic drugs can be escalated to treat Parkinsonian symptoms, whereas selective dopamine blockers can be added to block psychosis. Old management strategies required a reduction in dopaminergic therapy and therefore worsened Parkinsonian symptoms. Even though there have been great advances in the medical options for symptomatic management of PD, there are still many unmet needs for this patient population.

Crucian GP, Okun MS. · University of Florida Department of Neurology, P.O. Box 100236, Gainesville, FL 32610-0236, USA. · Front Biosci. · Pubmed #12957858 No free full text.

Abstract: Parkinson's Disease (PD) has traditionally been viewed as primarily a disturbance of motor functioning, typically involving tremor, rigidity, hypokinesia, gait disturbance, and postural instability. More recently, decline in cognitive function has been recognized as a feature of PD. One prominent cognitive symptom of PD involves deficits on tasks of spatial ability. However, findings of visual-spatial deficits in individuals with PD have been inconsistent. There are several methodological issues in this area of research that potentially confound the interpretation of data and need to be taken into consideration, including subject characteristics (e.g., age, sex and education), duration of illness, the current level of disability, the presence of emotional depression, the current level of medications, and the presence of dementia. Further, the tests that have shown visual-spatial deficits in PD are often complex, showing sensitivity to other cognitive processes as well. Another problem in this area of research is the lack of a clear understanding of the brain mechanisms that underlie visual-spatial deficits in PD. One theory of cognitive dysfunction in PD suggests that these cognitive deficits are in some way related to disruption of frontal-basal ganglia neural circuits important in executive functions. However, frontal-basal ganglionic dysfunction does not appear to account entirely for the visual-spatial cognitive deficits seen in PD. Subtle differences in performance on executive function measures appear to dissociate individuals with frontal lobe damage from individuals with PD. Findings from two recent studies indicate that PD is indeed associated with deficits in visual-spatial ability. These findings also indicate that the relationship between visual-spatial ability and frontal-executive function in PD is likely complex, and that the visual-spatial deficits in PD may be sensitive to the sex of the individual with PD.

Okun MS, McDonald WM, DeLong MR. · Department of Neurology, Emory University, 1639 Pierce Dr, Suite 6000, Atlanta, GA 30322, USA. · Arch Neurol. · Pubmed #12020264 links to  free full text

Abstract: BACKGROUND: Many patients with Parkinson disease (PD) suffer from nonmotor symptoms including depression, anxiety, sexual dysfunction, decreased energy level, and an overall decline in quality of life. Comorbid depression, hypothyroidism, and sleep disorders may account for some, but not all, of these problems. Testosterone deficiency affects 20% to 25% of males over the age of 60 years in the general population and may cause signs and symptoms of the nonmotor symptoms seen in PD. We observed numerous patients with PD whose nonmotor symptoms were refractory to treatment. OBJECTIVE: To determine whether treatment of comorbid testosterone deficiency in male patients with PD can lead to improvements in refractory nonmotor symptoms. METHODS: Case studies were reviewed of the first 5 male patients who had PD with symptoms of testosterone deficiency who were treated in our clinic. All patients had low serum testosterone levels. Screening for testosterone deficiency symptoms using the St Louis Testosterone Deficiency Questionnaire was performed for 4 of the 5 patients. Additionally, to assess the prevalence of PD, total testosterone levels in 68 patients in our PD registry were sent for evaluation. RESULTS: Following testosterone replacement therapy, all 5 patients experienced significant improvements in their refractory nonmotor symptoms. Of 68 male patients with PD enrolled in our PD registry, 24 (35%) had plasma evidence of testosterone deficiency. We also noted that the risk of testosterone deficiency per decade was found to increase 2.8-fold per decade (P<.001), paralleling that which is found in the general elderly male population. CONCLUSIONS: The findings from this study reveal the heretofore unrecognized high prevalence of testosterone deficiency in elderly male patients with PD similar to that found in the general population. These symptoms, which may be refractory to antidepressants, anxiolytics, and antiparkinsonian medications, may respond to treatment with testosterone. More rigorous controlled studies will need to be undertaken to examine the treatment of this common comorbidity in male patients with PD.

Okun MS, Watts RL. · Department of Neurology, Emory University School of Medicine & Wesley Woods Geriatric Center, Atlanta, GA 30322, USA. · Neurology. · Pubmed #11909987 No free full text.

Abstract: Depression associated with Parkinson's disease (PD) is common and affects 25 to 40% of patients. Recognition of the signs and symptoms of depression associated with PD is essential for clinical practitioners. Treatment of depression in this subset of patients can have a direct and dramatic impact on functional disability and quality of life. A review of the literature concerning depression and depression associated with PD was undertaken, with specific attention given to disease mechanisms, clinical presentation, association with thyroid disease, and the principles of management and treatment. Specific signs and symptoms of depression can be easily identified in patients with PD. Practitioners should be aware of these signs and symptoms when diagnosing and treating depression associated with PD. Practitioners should also be aware of the pros and cons of each treatment option and should choose a therapy appropriate for each individual patient's needs. It is important to identify the features of depression associated with PD in order to render early diagnosis and institute practical and efficacious therapy.

Okun MS, Green J, Saben R, Gross R, Foote KD, Vitek JL. · University of Florida McKnight Brain Institute, Gainesville, Florida 32610, USA. · J Neurol Neurosurg Psychiatry. · Pubmed #14617726 links to  free full text

Abstract: The results of this study suggest that there are mood changes associated with deep brain stimulation of the subthalamic nucleus (STN) and the globus pallidus interna (GPi). Further, optimal placement of electrodes in both STN and GPi seems to result in overall improvement in mood and is associated with a lower incidence of adverse mood effects than stimulation outside the optimal site. Preliminary data from this study, however, suggest that slight movement dorsal or ventral to the site of optimal motor performance may be associated with more adverse changes in mood with STN stimulation than with GPi stimulation.

Okun MS, Foote KD. · Department of Neurology, University of Florida Movement Disorders Center, McKnight Brain Institute, PO Box 100236, Gainesville, FL 32610, USA. · Arch Neurol. · Pubmed #19506140 No free full text.

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Plowman-Prine EK, Okun MS, Sapienza CM, Shrivastav R, Fernandez HH, Foote KD, Ellis C, Rodriguez AD, Burkhead LM, Rosenbek JC. · Department of Neurology, University of Florida, Gainesville, FL 32610, USA. · NeuroRehabilitation. · Pubmed #19339752 No free full text.

Abstract: The purpose of this study was to: (1) define perceptual speech characteristics of idiopathic Parkinson disease (IPD) across 35 speech dimensions adapted from Darley et al. [19] and grouped under six speech-sign clusters (respiration, phonation, resonance, articulation, prosody and rate); (2) examine the effects of levodopa on the 35 perceptual speech dimensions and speech-sign clusters; and (3) to compare the relative effectiveness of levodopa on global motor functioning vs. speech production. Sixteen patients with IPD read the 'Grandfather Passage' both 'on' and 'off' levodopa. Three blinded speech-language pathologists performed perceptual speech analyses using a seven-point scale. The diagnosis of IPD was made by a movement disorders fellowship trained neurologist who applied UK Brain bank criteria and administered the Unified Parkinson Disease Rating Scale. Concordant with previous studies, the results of this experiment indicated that IPD disrupted multiple speech production subsystems, with prosody being the most severely affected domain. The perceptual dimensions that were most severely affected included: (1) sound imprecision; (2) mono-loudness; (3) mono-pitch; (4) reduced stress and (5) harsh voice. No significant differences were obtained between medicated states ('on'/'off') for any of the 35 individual speech dimensions and speech-sign clusters. Global motor function significantly improved following dopaminergic medications.

Shapiro MA, Chang YL, Munson SK, Jacobson CE, Rodriguez RL, Skidmore FM, Okun MS, Fernandez HH. · Department of Neurology, Movement Disorders Center, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, USA; · Neuropsychiatr Dis Treat. · Pubmed #19300546 links to  free full text

Abstract: Several studies have related pathological gambling in PD to dopamine agonist therapy. A mail-in survey was sent to PD patients seen at the University of Florida Movement Disorders Center to determine gambling frequency and behavior, and any lifestyle or environmental factors associated with compulsive gambling in PD. 462 surveys were sent and 127 completed surveys were returned, of which ten were from patients who met criteria for compulsive gambling. All ten were taking dopamine agonists coincident with the compulsive gambling. Compulsive gamblers were younger, and psychological distress measures revealed that compulsive gamblers exhibited higher levels of anxiety, anger, and confusion. Thus in this cohort, we have uncovered the several characteristics of the most likely PD compulsive gambler, namely: (young) age, "angry", "anxious", and using a (dopamine) agonist.

Okun MS, Fernandez HH, Wu SS, Kirsch-Darrow L, Bowers D, Bova F, Suelter M, Jacobson CE, Wang X, Gordon CW, Zeilman P, Romrell J, Martin P, Ward H, Rodriguez RL, Foote KD. · Movement Disorders Center, University of Florida, McKnight Brain Institute, College of Medicine, Department of Neurology, Gainesville, FL 32611, USA. · Ann Neurol. · Pubmed #19288469 No free full text.

Abstract: OBJECTIVE: Our aim was to compare in a prospective blinded study the cognitive and mood effects of subthalamic nucleus (STN) vs. globus pallidus interna (GPi) deep brain stimulation (DBS) in Parkinson disease. METHODS: Fifty-two subjects were randomized to unilateral STN or GPi DBS. The co-primary outcome measures were the Visual Analog Mood Scale, and verbal fluency (semantic and letter) at 7 months post-DBS in the optimal setting compared to pre-DBS. At 7 months post-DBS, subjects were tested in four randomized/counterbalanced conditions (optimal, ventral, dorsal, and off DBS). RESULTS: Forty-five subjects (23 GPi, 22 STN) completed the protocol. The study revealed no difference between STN and GPi DBS in the change of co-primary mood and cognitive outcomes pre- to post-DBS in the optimal setting (Hotelling's T(2) test: p = 0.16 and 0.08 respectively). Subjects in both targets were less "happy", less "energetic" and more "confused" when stimulated ventrally. Comparison of the other 3 DBS conditions to pre-DBS showed a larger deterioration of letter verbal fluency in STN, especially when off DBS. There was no difference in UPDRS motor improvement between targets. INTERPRETATION: There were no significant differences in the co-primary outcome measures (mood and cognition) between STN and GPi in the optimal DBS state. Adverse mood effects occurred ventrally in both targets. A worsening of letter verbal fluency was seen in STN. The persistence of deterioration in verbal fluency in the off STN DBS state was suggestive of a surgical rather than a stimulation-induced effect. Similar motor improvement were observed with both STN and GPi DBS.

Mann JM, Foote KD, Garvan CW, Fernandez HH, Jacobson CE, Rodriguez RL, Haq IU, Siddiqui MS, Malaty IA, Morishita T, Hass CJ, Okun MS. · Department of Neurology, University of Florida College of Medicine/Shands Hospital, Movement Disorders Center, McKnight Brain Institute, Gainesville, Florida 32610, USA. · J Neurol Neurosurg Psychiatry. · Pubmed #19237386 No free full text.

Abstract: OBJECTIVE: To determine how intraoperative microelectrode recordings (MER) and intraoperative lead placement acutely influence tremor, rigidity, and bradykinesia. Secondarily, to evaluate whether the longevity of the MER and lead placement effects were influenced by target location (subthalamic nucleus (STN) or globus pallidus interna (GPi)). BACKGROUND: Currently most groups who perform deep brain stimulation (DBS) for Parkinson disease (PD) use MER, as well as macrostimulation (test stimulation), to refine DBS lead position. Following MER and/or test stimulation, however, there may be a resultant "collision/implantation" or "microlesion" effect, thought to result from disruption of cells and/or fibres within the penetrated region. These effects have not been carefully quantified. METHODS: 47 consecutive patients with PD undergoing unilateral DBS for PD (STN or GPi DBS) were evaluated. Motor function was measured at six time points with a modified motor Unified Parkinson Disease Rating Scale (UPDRS): (1) preoperatively, (2) immediately after MER, (3) immediately after lead implantation/collision, (4) 4 months following surgery-off medications, on DBS (12 h medication washout), (5) 6 months postoperatively-off medication and off DBS (12 h washout) and (6) 6 months-on medication and off DBS (12 h washout). RESULTS: Significant improvements in motor scores (p<0.05) (tremor, rigidity, bradykinesia) were observed as a result of MER and lead placement. The improvements were similar in magnitude to what was observed at 4 and 6 months post-DBS following programming and medication optimisation. When washed out (medications and DBS) for 12 h, UPDRS motor scores were still improved compared with preoperative testing. There was a larger improvement in STN compared with GPi following MER (p<0.05) and a trend for significance following lead placement (p<0.08) but long term outcome was similar. CONCLUSION: This study demonstrated significant acute intraoperative penetration effects resulting from MER and lead placement/collision in PD. Clinicians rating patients in the operating suite should be aware of these effects, and should consider pre- and post-lead placement rating scales prior to activating DBS. The collision/implantation effects were greater intraoperatively with STN compared with GPi, and with greater disease duration there was a larger effect.

Won MS, Mikos A, Hurd M, Fernandez H, Eskin T, Romrell J, Okun MS. · Department of Neurology, Movement Disorders Center, McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA. · Neurocase. · Pubmed #19235627 No free full text.

Abstract: We describe a case of tardive parkinsonism in the setting of bipolar syndrome, and we offer pathological confirmation that idiopathic Parkinson disease was not the underlying etiology. A 74-year-old Hispanic woman with a history of bipolar disease was noted to have oro-buccal-lingual chorea and parkinsonian symptoms such as resting tremor, rigidity, bradykinesia, and gait disorder persisting several months after neuroleptic discontinuation. She had minor improvement in ambulation with levodopa treatment, and she significantly improved in ambulation only during her manic states. Examination of the subject's post-mortem brain revealed no explicit evidence of degeneration in substantia nigra or other brainstem centers, and no nigral or cortical Lewy bodies were present. Glial cytoplasmic inclusions (characteristic of multiple systems atrophy) and globose neurofibrillary tangles (seen in progressive supranuclear palsy) were not seen either. This patient's presentation was most consistent with neuroleptic-induced parkinsonism and tardive dyskinesia; the etiology was likely related to previous neuroleptic exposure.

Mikos AE, Springer US, Nisenzon AN, Kellison IL, Fernandez HH, Okun MS, Bowers D. · Department of Clinical and Health Psychology, University of Florida, Gainesville, FL 32601, USA. · Clin Neuropsychol. · Pubmed #19169938 No free full text.

Abstract: A masked facial expression, one of the hallmark features of Parkinson disease (PD), can form the basis for misattributions by others about a patient's mood or interest levels. Reports of preserved intensity of internal emotional experience in PD participants raise the question of whether patients are aware of their outward expressivity levels. The aim of the present study was to determine whether PD participants exhibit deficits in overall emotional expressivity, and if so, whether they are aware of these deficits. We evaluated 37 non-demented PD participants and 21 comparison participants using the Berkeley Expressivity Questionnaire (BEQ). To examine awareness of emotional expressivity, we compared participant self-ratings of their own expressivity to ratings made by family members or close friends. Participants also completed questionnaires regarding depression and apathy and underwent motor examination and cognitive screening. PD participants' self-ratings of emotional expressivity were significantly lower than comparison participants' self-ratings. Even so, the PD participants viewed themselves as experiencing equivalent levels of emotional intensity to comparison participants, based on analysis of the BEQ subscales. Informant and PD participant self-ratings did not differ, indicating that PD participants accurately appraise the extent of their reduced expressivity. These findings suggest that anosognosia for emotional expressivity is not a prominent feature of nondemented Parkinson disease. Importantly, PD participants are aware of their reduced expressivity and report experiencing emotions as intensely as comparison participants. These findings highlight the view that diminished emotional expressivity in PD should not be mistaken for decreased subjective emotional experience.

Zahodne LB, Young S, Kirsch-Darrow L, Nisenzon A, Fernandez HH, Okun MS, Bowers D. · Department of Clinical & Health Psychology, University of Florida, Gainesville, Florida 32610-0165, USA. · Mov Disord. · Pubmed #19133658 No free full text.

Abstract: Apathy is a unique, multidimensional syndrome commonly encountered in patients with Parkinson disease (PD). Recently, the Lille Apathy Rating Scale (LARS), a semistructured interview yielding a global score, and composite subscores for different domains of apathy (i.e., cognitive, behavioral, affective, self awareness), was developed and given to a sample of patients with PD in France. This study is the first outside of its original developers to examine the English language version of the LARS in PD. We found the LARS to be a coherent instrument demonstrating both convergent and divergent validity, as compared to the Apathy Scale (AS) and Beck Depression Inventory (BDI-II). Using a receiver operating characteristic (ROC) analysis comparing the LARS to the AS, a validated and widely-used measure, we identified a cut-off score (sensitivity = 64%, specificity = 92%, PPV = 88%, NPV = 75%) that was higher than that proposed by the original authors, who derived their cut-off by comparing LARS global scores to clinical judgments of apathy. Although the present study does not compare the LARS to a diagnostic gold standard or promote its utility for diagnosing apathy, it provides further support for the LARS as a promising instrument to examine apathy in PD.

Marino SE, Meador KJ, Loring DW, Okun MS, Fernandez HH, Fessler AJ, Kustra RP, Miller JM, Ray PG, Roy A, Schoenberg MR, Vahle VJ, Werz MA. · Experimental and Clinical Pharmacology, University of Minnesota, 717 Delaware Street SE, Room 517, Minneapolis, MN 55414, USA. · Epilepsy Behav. · Pubmed #19130899 No free full text.

Abstract: OBJECTIVE: Clinicians monitor cognitive effects of drugs primarily by asking patients to describe their side effects. We examined the relationship of subjective perception of cognition to mood and objective cognitive performance in healthy volunteers and neurological patients. METHODS: Three separate experiments used healthy adults treated with lamotrigine (LTG) and topiramate (TPM), adults with epilepsy on LTG or TPM, and patients with idiopathic Parkinson's disease. Correlations were calculated for change scores on and off drugs in the first two experiments and for the single assessment in Experiment 3. RESULTS: Across all three experiments, significant correlations were more frequent (chi(2)=259, P < or = 0.000) for mood versus subjective cognitive perception (59%) compared with subjective versus objective cognition (2%) and mood versus objective cognitive performance (2%). CONCLUSIONS: Subjective perception of cognitive effects is related more to mood than objective performance. Clinicians should be aware of this relationship when assessing patients' cognitive complaints.