Quantitative EEG as a predictive biomarker for Parkinson disease dementia.

OBJECTIVE: We evaluated quantitative EEG (QEEG) measures as predictive biomarkers for the development of dementia in Parkinson disease (PD). Preliminary work shows that QEEG measures correlate with current PD cognitive state. A reliable predictive QEEG biomarker for PD dementia (PD-D) incidence would be valuable for studying PD-D, including treatment trials aimed at preventing cognitive decline in PD. METHODS: A cohort of subjects with PD in our brain donation program utilizes annual premortem longitudinal movement and cognitive evaluation. These subjects also undergo biennial EEG recording. EEG from subjects with PD without dementia with follow-up cognitive evaluation was analyzed for QEEG measures of background rhythm frequency and relative power in δ, , α, and ß bands. The relationship between the time to onset of dementia and QEEG and other possible predictors was assessed by using Cox regression. RESULTS: The hazard of developing dementia was 13 times higher for those with low background rhythm frequency (lower than the grand median of 8.5 Hz) than for those with high background rhythm frequency (p < 0.001). Hazard ratios (HRs) were also significant for > median bandpower (HR = 3.0; p = 0.004) compared to below, and for certain neuropsychological measures. The HRs for δ, α, and ß bandpower as well as baseline demographic and clinical characteristics were not significant. CONCLUSION: The QEEG measures of background rhythm frequency and relative power in the band are potential predictive biomarkers for dementia incidence in PD. These QEEG biomarkers may be useful in complementing neuropsychological testing for studying PD-D incidence.

Medication dose reductions after pallidal versus subthalamic stimulation in patients with Parkinson's disease.

OBJECTIVE: To compare the medication dose reduction between deep brain stimulation (DBS) of the globus pallidus interna (GPi) vs subthalamic nucleus (STN) in matched patients with Parkinson's disease (PD). MATERIALS AND METHODS: Records of 12 patients with PD who underwent GPi-DBS at our institution from 2002 to 2008 were matched by pre-operative PD medication doses and pre-operative motor Unified Parkinson's Disease Rating Scale (UPDRS) scores to 12 cases of STN-DBS. PD medication doses were converted to levodopa equivalent doses (LEDs). RESULTS: GPi and STN groups had similar mean pre-operative LEDs and motor UPDRS scores. At 6 months post-DBS, there was no significant difference in percent reduction in LEDs between the GPi (47.95%) and STN (37.47%) groups (P = 0.52). The mean post-operative 'medication off/stimulation on' motor UPDRS scores did not differ significantly between GPi (15.33) and STN (16.25) groups (P = 0.74). The mean percent reduction in motor UPDRS scores was also similar between GPi (58.44%) and STN (58.98%) patients (P = 0.94). CONCLUSIONS: We conclude that in disease-matched patients with PD undergoing DBS, both GPi and STN may result in similar reduction in PD medication doses.

Functional ability correlates with cognitive impairment in Parkinson's disease and Alzheimer's disease.

BACKGROUND/AIMS: Previously we have shown that functional declines in Parkinson's disease (PD) and Alzheimer's disease (AD) correlate to global measures of cognitive decline. We now determine if the correlation between cognitive impairment and functional ability in PD is similar to that in AD using individual cognitive measures. METHODS: 93 PD subjects and 124 AD/MCI subjects underwent the Functional Assessment Staging (FAST), the Global Deterioration Scale (GDS), and a neuropsychological battery. RESULTS: In PD subjects, the FAST and GDS correlated significantly with Rey Auditory Verbal Learning Test (AVLT), Controlled Oral Word Association (COWA), Animal Fluency, and Stroop but not with Clock Draw or Judgment Line Orientation (JLO). In AD/MCI subjects, FAST and GDS correlated with all neuropsychological components except Stroop. In the AD/MCI group, the UPDRS significantly correlated with the FAST, GDS, MMSE, and all neuropsychological parameters except the Stroop. In the PD group, the motor UPDRS significantly correlated significantly with FAST, GDS, MMSE and all neuropsychological parameters except Digit Span, Stroop, Clock Draw and JLO. CONCLUSIONS: Similar to AD, functional decline in PD correlates with multiple measures of cognitive impairment. Some differences between PD and AD may be explained by the influence of motor disability and declines in visuospatial function in PD.

Both early and late cognitive dysfunction affects the electroencephalogram in Parkinson's disease.

We sought to define quantitative electroencephalographic (EEG) measures as biomarkers of both early and late cognitive decline in Parkinson's disease (PD). PD subjects classified as cognitively normal (PD-CogNL), mild cognitive impairment (PD-MCI), and dementia (PD-D) were studied. Cognitive status and neuropsychological testing was correlated with background rhythm and frequency band EEG power across five frequency bands. We conclude that global EEG measures have potential use as biomarkers in the study of both early and late cognitive deterioration in PD, including for evaluating its treatment. PD-MCI has mean quantitative EEG characteristics that represent an intermediate electrophysiological state between PD-CogNL and PD-D.

An autosomal dominant ataxia maps to 19q13: Allelic heterogeneity of SCA13 or novel locus?

The autosomal dominant spinocerebellar ataxias (ADCAs) represent a growing and heterogeneous disease phenotype. Clinical characterization of a three-generation Filipino family segregating a dominant ataxia revealed cerebellar signs and symptoms. After elimination of known spinocerebellar ataxia (SCA) loci, a genome-wide linkage scan revealed a disease locus in a 4-cM region of 19q13, with a 3.89 lod score. This region overlaps and reduces the SCA13 locus. However, this ADCA is clinically distinguishable from SCA13.

Persistent chorea triggered by hyperglycemic crisis in diabetics.

Five female patients developed chorea concurrent with, or shortly after a hyperglycemic episode (admission glucose values 500-1,000 mg/dL). In four of these five patients, there was no prior history of diabetes mellitus. The chorea continued despite correction of blood glucose and persisted to the time of last follow-up, 6 months to 5 years later. The chorea developed subacutely over 2 days to 1 month and was generalized in one, unilateral in three, and involved right > left lower extremity in the other; the severity initially reached ballistic proportions in two. Associated clinical features were nil in four of these patients, but cognitive impairment and personality change occurred in one. The histories and laboratory studies identified no predisposing factors other than the hyperglycemia. The chorea was sufficiently troublesome to require administration of neuroleptic medication in all five cases. Four of the five cases had high signal intensity within basal ganglia on T1-weighted magnetic resonance (MR) imaging, as has previously been described; however, this was not seen in one case (who had the most severe clinical condition). Most previously described cases have involved a reversible clinical syndrome, in contrast to our patients. The pathogenic mechanisms remain uncertain.

Serum leptin concentrations and satiety in Parkinson's disease patients with and without weight loss.

We compared serum leptin and satiety measures in 18 Parkinson's disease (PD) patients with unintended weight loss (WL) and 18 PD patients whose weight was stable (WS). Mean serum leptin concentrations tended to be lower in WL than WS patients, but this did not reach statistical significance. Body mass index correlated with serum leptin concentrations. Ratings of hunger, satiety, fullness, and thirst did not differ between groups. However, the mean sensation of fullness before meals correlated with serum leptin in the entire cohort of patients, particularly in the WL group. The results indicate that unintended weight loss in PD patients is unlikely to be due to abnormal serum leptin concentrations.

Piribedil for restless legs syndrome: a pilot study.

Thirteen consecutive patients with restless legs syndrome (RLS) were treated with piribedil and were rated using an RLS rating scale (0-10) and subjective response (0-100%); 11/13 (85%) had improvement of their mean RLS scores with subjective response ranging from 30% to 100% (mean 74.6%). This pilot study suggests that piribedil is effective for RLS.

The effect of temperature on hand function in patients with tremor.

Hand therapists may notice a patient's tremor when treating another diagnostic problem, such as arthritis or a fracture. In these instances, the tremor may become apparent as the patient attempts to don or doff a splint or to practice a home exercise program, or it may be reported in terms of difficulty with dressing or eating. The authors hypothesized that limb cooling would temporarily improve hand function among patients with essential tremor (ET) and that limb warming would temporarily improve hand function among patients with resting tremor secondary to Parkinson disease (PD). Twenty patients with ET and 20 patients with PD completed this single-blind randomized crossover study. Scores following exposure to cold water were compared with scores following exposure to warm water. For patients with ET, subtest scores for the Archimedes spiral, simulated feeding, and checkers were, statistically, significantly lower (i.e., improved) following exposure to cold water than following exposure to warm water; scores for Archimedes spiral card turning, simulated feeding, and checkers were significantly lower following exposure to cold water than at baseline. Scores for Archimedes spiral and card turning were also significantly lower following exposure to warm water than at baseline. For patients with PD, no statistically significant differences were noted between treatments or from baseline except the score for small common objects, which was lower (improved) following exposure to warm water than at baseline. The significant findings from this study support the therapeutic use of cooling to temporarily decrease tremor, thereby improving hand function among patients with ET.

Understanding essential tremor. Differential diagnosis and options for treatment.

Although essential tremor is common, its various presentations may be confused with other movement disorders, such as Parkinson's disease and dystonic tremor. In this article, Dr Evidente describes classification of tremor, the clinical features of essential tremor, and the differential diagnostic considerations. He also discusses the extensive list of medications used to treat the disorder and the surgical options for severe, drug-resistant cases.

Is it a tic or Tourette's? Clues for differentiating simple from more complex tic disorders.

Tics are characterized by sterotyped, purposeless, and irregularly repetitive movements and usually can be classified as chronic motor or vocal tic disorders, transient tic disorders, or Tourette's syndrome. The latter is a complex disorder associated with multiple tics and often accompanied by other conditions, such as ADHD and obsessive-compulsive disorder. Treatment can be difficult, and drug therapy should begin with agents least likely to cause problems for the patient. Education of the patient and family and support from the physician and other care providers are essential elements of effective management.

Hereditary ataxias.

There are many causes of hereditary ataxia. These can be grouped into categories of autosomal recessive, autosomal dominant, and X-linked. Molecularly, many of them are due to trinucleotide repeat expansions. In Friedreich ataxia, the trinucleotide repeat expansions lead to a "loss of function." In the dominant ataxias, the expanded repeats lead to a "gain of function," most likely through accumulation of intranuclear (and less commonly cytoplasmic) polyglutamine inclusions. Channelopathies can also lead to ataxia, especially episodic ataxia. Although phenotypic characteristics are an aid to the clinician, a definitive diagnosis is usually made only through genotypic or molecular studies. Genetic counseling is necessary for the testing of symptomatic and asymptomatic individuals. No effective treatment is yet available for most ataxic syndromes, except for ataxia with isolated vitamin E deficiency and the episodic ataxias.

Amantadine is beneficial in restless legs syndrome.

Twenty-one patients (mean age 70 yrs) with restless legs syndrome (RLS) were treated with amantadine in an open-label trial. Amantadine was started at 100 mg per day and was increased every 3-5 days by 100 mg (up to a maximum of 300 mg per day) until significant relief of symptoms or intolerable side effects were experienced. Patients were rated pre- and posttreatment using an RLS rating scale (0-10). Each patient also rated the degree of response in a continuous scale from 0% (no improvement) to 100% (complete improvement). Eleven of 21 (52%) had subjective benefit to amantadine, with degree of response ranging from 25%-100% (mean 69%) among responders. Six had 95%-100% improvement. The RLS score for all 21 patients dropped from a mean (+/- standard deviation) of 9.8 +/- 0.6 (range, 8-10) pretreatment to 6.6 +/- 3.8 (range, 0-10) posttreatment (p = 0.001). The duration of response was 0-13 months (mean, 3.6 +/- 4.5), with nine responders still remaining on the drug as of last follow up. The mean effective dose was 227 mg per day. The most common side effects were drowsiness (3), fatigue (2), and insomnia (2); only two stopped amantadine because of side effects. We conclude that amantadine is an effective and well-tolerated drug for RLS.

Intersubject variability and intrasubject reproducibility of the bereitschaftspotential.

We assessed the intersubject variability and intrasubject reproducibility of the bereitschaftspotential (BP). Twenty healthy volunteers performed extensions of their wrist in a self-paced manner every 5-10 seconds. A surface electromyography (EMG) electrode was attached to the wrist extensor group of the dominant hand to record at least 100 wrist movements, and electroencephalography electrodes were placed over the scalp. Trials were performed at baseline, 15 minutes, 4 hours, and 4 weeks. Measures derived from the BP included area 1 (-2000 to -650 msec), area 2 (-650-0 msec), total area (area 1 + area 2), amplitude at -650 msec, amplitude at peak negativity prior to EMG onset, and amplitude at 0 msec (trigger). Our findings revealed different variability/reproducibility depending on the particular BP measure being analyzed. Using intraclass correlation coefficient (ICC) and concordance correlation coefficient (CCC) as measures of intrasubject reproducibility, area 2, amplitude at peak negativity prior to EMG onset, and amplitude at 0 msec produced the best values. We conclude that in studies that attempt to quantify BP changes before and after an intervention in the same group of subjects, the most reproducible BP measures are those pertaining to the late BP component.

How to help patients with restless legs syndrome. Discerning the indescribable and relaxing the restless.

Restless legs syndrome is a common, potentially disabling condition that affects about 10% to 15% of the general population and yet is often unrecognized and misdiagnosed. It is mainly diagnosed clinically and only rarely requires polysomnography. The condition is usually primary and treatable. First, however, secondary causes should be sought, especially iron deficiency and peripheral neuropathy, because when the source is an accompanying factor or condition, the syndrome may be curable. The most effective drugs are dopaminergic agents, clonazepam, opioids, gabapentin, and clonidine. Additional agents are available that may be beneficial as add-on or alternative therapy.

A pilot study on the motor effects of rimantadine in Parkinson's disease.

The purpose of this pilot study was to determine whether rimantadine, the alpha-methyl derivative of amantadine, might have any antiparkinsonian properties. In an open-label trial, 14 patients (12 de novo and 2 on levodopa treatment) with Hoehn and Yahr stage 2 to 3 Parkinson's disease were placed on rimantadine at doses of 100 to 300 mg/d. No patients had dyskinesias or motor fluctuations. Ten of 14 (71%) reported a mean subjective response of 33% (range 10%-60%) to rimantadine. After treatment, there was a 13% improvement in Hoehn and Yahr staging (p = .01) and a 20% improvement in mean motor Unified Parkinsons Disease Rating Scale scores (p = .02). Rigidity was the most consistently improved feature among the responders. Mean effective dose was 256 mg/d (range 200-300 mg/d). Side effects were mild and transient, with nausea being most common (4/14). We conclude that rimantadine has some motor benefits in Parkinson's disease. A double-blind placebo-controlled study is warranted to validate our findings.