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Biomedical subjects

William G Ondo

Publications and source records attributed to William G Ondo.

At least 19 recordsLinked to original sources
PubMed2007

G2019S mutation in the leucine-rich repeat kinase 2 gene is not associated with multiple system atrophy.

Multiple system atrophy (MSA) is characterized clinically by Parkinsonism, cerebellar dysfunction, and autonomic impairment. Multiple mutations in the LRRK2 gene are associated with parkinsonian disorders, and the most common one, the G2019S mutation, has been found in approximately 1% of sporadic cases of Parkinsonism. In a well-characterized cohort of 136 subjects with probable MSA and 110 neurologically evaluated control subjects, none carried the G2019S mutation. We conclude that the G2019S mutation in the LRRK2 gene is unlikely to be associated with MSA.

Cerebellum↗
PubMed2006

Long-term monitoring of gait in Parkinson's disease.

A new system for long-term monitoring of gait in Parkinson's disease (PD) has been developed and validated. The characteristics of every stride taken over 10-h epochs were acquired using a lightweight ankle-mounted sensor array that transmitted data wirelessly to a small pocket PC at a rate of 100 Hz. Stride was calculated from the vertical linear acceleration and pitch angular velocity of the leg with an accuracy of 5 cm. Results from PD patients (5) demonstrate the effectiveness of long-term monitoring of gait in a natural environment. The small, variable stride length characteristic of Parkinsonian gait, and fluctuations of efficacy associated with levodopa therapy, such as delayed onset, wearing off, and the 'off/on' effect, could reliably be detected from long-term changes in stride length.

Adult↗
PubMed2006

Heterogeneous phenotype in a family with compound heterozygous parkin gene mutations.

BACKGROUND: Mutations in the parkin gene (PRKN) cause autosomal recessive early-onset Parkinson disease (EOPD). OBJECTIVE: To investigate the presence of mutations in the PRKN gene in a white family with EOPD and the genotype-phenotype correlations. DESIGN: Twenty members belonging to 3 generations of the EOPD family with 4 affected subjects underwent genetic analysis. Direct genomic DNA sequencing, semiquantitative polymerase chain reaction, real-time quantitative polymerase chain reaction, and reverse-transcriptase polymerase chain reaction analyses were performed to identify the PRKN mutation. RESULTS: Compound heterozygous mutations (T240M and EX 5_6 del) in the PRKN gene were identified in 4 patients with early onset (at ages 30-38 years). Although heterozygous T240M and homozygous EX 5_6 del mutations in the PRKN gene have been previously described, this is, to our knowledge, the first report of these mutations in compound heterozygotes. The phenotype of patients was that of classic autosomal recessive EOPD characterized by beneficial response to levodopa, relatively slow progression, and motor complications. All heterozygous mutation carriers (T240M or EX 5_6 del) and a 56-year-old woman who was a compound heterozygous mutation carrier (T240M and EX 5_6 del) were free of any neurological symptoms. CONCLUSIONS: Compound heterozygous mutations (T240M and EX 5_6 del) in the PRKN gene were found to cause autosomal recessive EOPD in 4 members of a large white family. One additional member with the same mutation, who is more than 10 years older than the mean age at onset of the 4 affected individuals, had no clinical manifestation of the disease. This incomplete penetrance has implications for genetic counseling, and it suggests that complex gene-environment interactions may play a role in the pathogenesis of PRKN EOPD.

Adult↗
PubMed2006

Association between restless legs syndrome and essential tremor.

After observing that several families with essential tremor (ET) clinically cosegregated with restless legs syndrome (RLS), we prospectively evaluated for the presence of RLS in 100 patients presenting to the Baylor College of Medicine with ET and prospectively examined all patients presenting with RLS for the presence of tremor during the same time frame. Of 100 consecutive ET patients (60 women and 75 with a family history of ET) seen over 19 weeks (current age, 65.2 +/- 16.3 years; age at tremor onset, 37.8 +/- 19.9 years) 33 met all criteria for RLS, of which 25 had never been diagnosed previously. A family history of RLS was reported in 57.6% of these 33 patients and was the only significant predictor of RLS in the ET population. Their International Restless Legs Syndrome Rating Scale score was 16.6 +/- 8.1. Over 19 weeks, we also examined 68 consecutive RLS patients (63.2% women and 54.4% with a family history of RLS) for the presence of tremor. Their current age was 55.8 +/- 14.4 years, and age at RLS onset was 33.7 +/- 19.5 years. Overtly pathological tremor was rare, but trace tremor was very common. Overall, we found a very high rate of undiagnosed RLS in patients presenting for tremor, but unlike other "secondary" forms of RLS, this finding was also associated with a high familial history of RLS, suggesting that they share some genetic similarities.

Adolescent↗
PubMed2006

Subthalamic deep brain stimulation in patients with a previous pallidotomy.

The safety and efficacy of subthalamic nucleus (STN) deep brain stimulation (DBS) in patients who have had a previous unilateral pallidotomy is not clear. We identified 10 patients (9 male) at the Baylor College of Medicine Parkinson's Disease Center who underwent STN DBS after prior unilateral pallidotomy. Demographics, efficacy as determined by off Unified Parkinson's Disease Rating Scale (UPDRS) part III scores, and levodopa equivalent dosing were analyzed. We then compared these to an age- and sex-matched group of 25 DBS patients who had no prior pallidotomy. After their initial pallidotomy (mean age, 51.8 +/- 10.8 years), the mean UPDRS motor off medicine scores improved from 51.3 +/- 14.3 to 34.9 +/- 12.8, and the UPDRS dyskinesia score improved from 1.8 +/- 1.0 to 0.8 +/- 0.7. Their STN DBS off UPDRS motor scores (mean age, 56.0 +/- 10.2 years) improved by 16.0% from 53.1 +/- 9.7 (range, 42-68) to 44.6 +/- 11.1 (range, 25-67). In contrast, the UPDRS off motor scores in a control group of 25 DBS patients improved by 49.9%, from 49.7 +/- 11.1 to 25.7 +/- 18.9, (16.0% vs. 49.9%; P < 0.001). Changes in UPDRS dyskinesia scores were similar in both groups. AE thought to be related to the STN DBS following pallidotomy included worse dysarthria (three) and worse balance (two). STN DBS patients with prior pallidotomy had less improvement in UPDRS off motor score compared to other STN DBS patients, despite relatively good outcomes immediately after their pallidotomy. This may be partially due to a selection bias, but it may also indicate that prior pallidotomy is a negative predictor of outcome of STN DBS and should be considered in patient selection.

Adult↗
PubMed2006

Intravenous flumazenil for Parkinson's disease: a single dose, double blind, placebo controlled, cross-over trial.

Flumazenil is a short-acting intravenously administered gamma-aminobutyric acid (GABA) antagonist used to reverse the effects of benzodiazepines. Based upon current basal ganglion models in Parkinson's disease (PD), flumazenil could normalize neuronal signaling at several different locations. We conducted a double-blind, placebo controlled, single dose, cross-over trial of flumazenil and placebo in 16 subjects with PD. Subjects were primarily assessed with serial tapping tests (1 minute for each hand) at 15-minute intervals for 90 minutes after infusion. Secondary assessments included the Unified Parkinson's Disease Rating Scale (UPDRS) Motor part at baseline and 45 minutes after infusion, and global impressions. Subjects then underwent a 90-minute washout and entered the opposite arm of the cross-over. Change in tapping speed compared to baseline improved throughout the 90-minute period (P < 0.0001) and at each individual time (P < 0.01), except for 15 minutes status after infusion, with flumazenil compared to placebo. UPDRS scores tended to improve more on drug, but this finding was not significant. The medication was well tolerated. The most common adverse event on drug was a sense of "light-headedness" or "dizziness." GABA antagonists represent a novel potential treatment class for PD.

Adult↗
PubMed2006

Open-label flexible-dose pilot study to evaluate the safety and tolerability of aripiprazole in patients with psychosis associated with Parkinson's disease.

Psychosis affects at least 5% to 8% of medication-treated patients with idiopathic Parkinson's disease (PD). Treatment options include reducing medications used for the treatment of PD-related motor symptoms or introducing an atypical antipsychotic drug. Only clozapine has been demonstrated to be efficacious and tolerated in double-blind controlled trials. This study evaluated the effect of aripiprazole, an atypical antipsychotic, on psychosis in PD in an open-label pilot study. Fourteen patients meeting entry criteria were started on aripiprazole 1 mg/day and titrated up to a maximum dose of 5 mg as needed. Subjects were evaluated on the Unified Parkinson's Disease Rating Scale (UPDRS) part III for motor function, the Neuropsychiatric Inventory (NPI), and the Brief Psychiatric Rating Scale (BPRS) for psychiatric response. Statistically significant improvement in mean BPRS and positive BPRS subscales occurred with open-label aripiprazole, but eight subjects discontinued the study due to worsened Parkinsonism (three), worsened psychosis (two), worsening of both (two), and lack of efficacy (one). While some patients had a favorable response, aripiprazole was associated with an exacerbation of motor symptoms. In this small study on psychosis in PD, aripiprazole did not appear promising.

Aged↗
PubMed2006

Tetrabenazine for hyperglycemic-induced hemichorea-hemiballismus.

We reported a 74-year-old woman with new-onset diabetes mellitus who presented with the sudden onset of mild left hemiparesis and marked left hemichorea-hemiballismus. Brain CT scan and MRI showed T1W, T2W, and DWI lesions in the right putamen and caudate, which have been previously reported in cases of hyperglycemic-induced hemichorea-hemiballismus (HIHH). The patient dramatically responded to tetrabenazine within a day. Subsequent dose reductions lead to a reemergence of symptoms. Tetrabenazine improves a variety of hyperkinetic movement disorders but, to our knowledge, its use has never been reported for HIHH.

Aged↗
PubMed2006

Computerized posturography balance assessment of patients with bilateral ventralis intermedius nuclei deep brain stimulation.

Bilateral ventralis intermedius nuclei (Vim) deep brain stimulation (DBS) improves tremor in patients with both essential tremor (ET) and Parkinson's disease (PD). In each condition, patients have individually noted both subjective improvement and worsening in balance. Computerized posturography (CP) is able to quantify some aspects of balance. Twenty-one patients (8 with PD and 13 with ET) with bilateral Vim DBS were recruited to undergo randomized-order identical CP testing (EquiTest system) while their DBS devices were both activated and deactivated. One PD patient could not complete any OFF assessment and is not included. Three PD patients could not tolerate portions of the OFF testing. Overall, sensory organization testing was improved by DBS activation in conditions that involved quiet standing with eyes open with no motion of the support surface, or with sway-referenced support surface motion, but worsened during quiet standing with eyes closed only in ET patients. Falls lessened with activation in ET patients. Motor control testing was not changed. Bilateral Vim DBS activation mostly improved balance, but may modestly worsen other specific features.

Aged↗
PubMed2006

Essential tremor: treatment options.

The treatment of essential tremor depends on the tremor severity, location, and risk benefit ratios. Mild to moderate tremor usually will respond to oral agents such as noncardiac selective beta-blockers or primidone. Other agents including ethanol, topiramate, benzodiazepines, gabapentin, levetiracetam, and zonisamide may be effective. There are very little data comparing different oral agents, but there is support for polypharmacy in some cases. Botulinum toxin injections are effective in some tremor patterns, especially wrist flexion/extension and head tremor. For severe tremor, surgical lesioning or deep brain stimulation of the thalamus is justified and often dramatically improves function.

Journal Article↗
PubMed2006

Long-term evaluation of deep brain stimulation of the thalamus.

OBJECT: The effects of thalamic deep brain stimulation (DBS) on essential tremor (ET) and Parkinson disease (PD) have been well documented, but there is a paucity of long-term data. The aim of this study was to evaluate the long-term safety and efficacy of DBS of the ventralis intermedius nucleus (VIM) of the thalamus for PD and ET. METHODS: Thirty-eight of 45 patients enrolled at five sites completed a 5-year follow-up study. There were 26 patients with ET and 19 with PD undergoing 29 unilateral (18 ET/11 PD) and 16 bilateral (eight ET/eight PD) procedures. Patients with ET were evaluated using the Tremor Rating Scale, and patients with PD were evaluated using the Unified Parkinson's Disease Rating Scale. The mean age of patients with ET was 70.2 years and 66.3 years in patients with PD. Unilaterally implanted patients with ET had a 75% improvement of the targeted hand tremor; those with bilateral implants had a 65% improvement in the left hand and 86% in the right compared with baseline. Parkinsonian patients with unilateral implants had an 85% improvement in the targeted hand tremor and those with bilateral implants had a 100% improvement in the left hand and 90% improvement in the right. Common DBS-related adverse events in patients receiving unilateral implants were paresthesia (45%) and pain (41%), and in patients receiving implants bilaterally dysarthria (75%) and balance difficulties (56%) occurred. Device-related surgical revisions other than IPG replacements occurred in 12 (27%) of the 45 patients. CONCLUSIONS: Thalamic stimulation is safe and effective for the long-term management of essential and Parkinsonian tremors. Bilateral stimulation can cause dysarthria and incoordination and should be used cautiously.

Activities of Daily Living↗
PubMed2005

The North American survey of placement and adjustment strategies for deep brain stimulation.

BACKGROUND: Deep brain stimulation (DBS) is gaining wide acceptance as treatment for Parkinson's disease (PD), essential tremor, and dystonia. METHODS: A 40-item questionnaire commissioned by the DBS Study Group was sent to 46 centers that had performed at least 25 DBS implantations. These centers were identified through the DBS Study Group, other professional societies, and with the assistance of the Medtronic Corporation. The results were then tabulated and descriptive analyses were performed. RESULTS: Thirty-six of 47 centers (77%) responded, they had implanted 4,553 patients. The timing for bilaterally implanted patients varied, as 13 sites almost always implanted simultaneously whereas 14 sites almost never implanted simultaneously. Stereotactic frames included Leksell (n = 19), CRW (n = 15) and Compass (n = 2). Post-placement imaging was routinely performed by almost all centers and included MRI (n = 23), CT (n = 4), CT/MRI variably (n = 5), and ventriculography (n = 1). Two centers used more than one electrode per side. The 34 centers that used a single electrode averaged 2.3 +/- 1.4 passes per electrode (range: 1-18 passes). Most centers used macro-stimulation to confirm placement by assessing the intra-operative clinical response (n = 34), and to assess for adverse events (n = 26) at high voltages, averaging 6.7 +/- 2.3 V (range: 4-10). The initial activation averaged 18 +/- 12 days after electrode placement (average range: 11 +/- 10 to 28 +/- 18 days, absolute range: 1-90 days). Most sites had several programmers; however, the primary programmers were neurology staff (n = 15), the neurologist (n = 13), neurosurgery staff (n = 6), the neurosurgeon (n = 2), or a physiatrist (n = 1). Twelve centers automatically reduced PD medications on the day of initial activation, 9 centers reduced them variably, and 16 centers initially did not reduce them. Eventually, 80.4% of patients were reported to have some dose reduction, and 47.1% had a greater than 50% reduction of PD medications. CONCLUSIONS: Strategies regarding DBS placement and adjustment vary in North America.

Antiparkinson Agents↗
PubMed2005

Methadone for refractory restless legs syndrome.

Most cases of restless legs syndrome (RLS) initially respond well to dopaminergic agonists. However, an unknown percentage of patients is intolerant of dopaminergic adverse events, initially or subsequently refractory, or develops limiting augmentation. We administered methadone 5 to 40 mg/day (final dose, 15.6 +/- 7.7) to 29 RLS patients who failed dopaminergics. They were currently taking or had previously tried 5.9 +/- 1.7 (range, 3-9) different medications for RLS and 2.9 +/- 0.8 (range, 2-4) different dopaminergics. Of the 27 patients who met inclusion criteria, 17 have remained on methadone for 23 +/- 12 months (range, 4-44 months) at a dose of 15.5 +/- 7.7 mg/day; 2 dialysis RLS patients died while on methadone, and 8 stopped the treatment (5 for adverse events, 2 for lack of efficacy, and 1 for logistical reasons). All patients who remain on methadone report at least a 75% reduction in symptoms, and none have developed augmentation. Methadone should be considered in RLS patients with an unsatisfactory dopaminergic response.

Adult↗
PubMed2005

Olfaction testing in patients with tremor-dominant Parkinson's disease: is this a distinct condition?

There is considerable controversy regarding the relationship between essential tremor (ET) and Parkinson's disease (PD), especially when tremor is the dominant feature of PD or there is a family history of tremor. Reduced olfaction function is one of the initial signs of PD. In contrast, ET has relatively preserved olfaction. To infer whether the tremor-dominant subgroup of PD is intrinsically different from mainstream PD, we tested olfaction using the University of Pennsylvania Smell Identification Test-40 (UPSIT) in this group and compared the findings with those of patients with non-tremor-dominant "regular" PD. We then evaluated predictors of reduced UPSIT scores within the tremor-dominant group. Overall, olfaction did not differ between tremor-dominant PD and regular PD; however, the subgroup of tremor-dominant PD with a family history of tremor had less olfaction loss than those without a family history (P = 0.0007) or those with regular PD (P = 0.0350). Other clinical features of this tremor-dominant PD with a family history of tremor group mostly resembled those without a family history. This finding suggests that patients with a family history of tremor may represent a different disease process even though, aside from differences in olfaction, they are clinically similar to other patients with tremor-dominant parkinsonism. It additionally suggests phenotypic overlap between PD and ET.

Aged↗
PubMed2005

Double-blind, placebo-controlled, unforced titration parallel trial of quetiapine for dopaminergic-induced hallucinations in Parkinson's disease.

We completed a single site, double-blind, placebo-controlled, parallel design study of quetiapine for hallucinations in PD. Thirty-one subjects with PD and prominent visual hallucinations and Mini-Mental State Examination score >21 were randomly assigned in a 2:1 drug to placebo ratio, up to 200 mg daily of quetiapine or matching placebo given in two doses. They were seen at 3 weeks (100 mg/day) and 12 weeks (200 mg/day, with optional dose reduction). Evaluation included the Unified Parkinson's Disease Rating Scale (UPDRS), the Baylor PD Hallucination Questionnaire, and a battery of neuropsychological tests. The demographics between subjects randomized to drug (n = 21) vs. placebo (n = 10) were similar. The final dose of active drug was 200 (n = 11), 150 (n = 2), 100 (n = 3), and 75 (n = 1) mg per day. All placebo subjects were on the equivalent of 200 mg per day. The UPDRS Activities of Daily Living and Motor scores did not significantly change compared to placebo. Compared to placebo, there were no significant changes in our hallucination questionnaire, the Brief Psychiatric Rating Scale (BPRS), or question 12 (hallucination item) of the BPRS. There were no significant changes on any of the neuropsychological measures. Adverse events on drug included sedation (n = 9), but no drug-related adverse events precipitated discontinuation and none were rated as serious. Quetiapine, up to 200 mg daily, was well tolerated and did not worsen UPDRS scores; however, there was no significant improvement in psychosis rating scales compared to placebo. Larger doses of drug and greater sample sizes might be considered in future studies.

Adult↗
PubMed2005

Restless legs syndrome.

Restless legs syndrome is a very common and still under-diagnosed neurologic condition that can cause severe morbidity. The pathology centers around central nervous system iron homeostatic dysregulation with subsequent alterations in dopaminergic functioning. Genetic studies will hopefully soon identify specific abnormalities. Treatment of restless legs syndrome with dopaminergic medications is highly effective, although augmentation may occur eventually and require dosing flexibility.

Brain↗
PubMed2005

Restless legs syndrome.

Restless legs syndrome (RLS) is clinically defined as an urge to move the legs with or without paresthesia, worsening of symptoms with rest and transient improvement with activity, and worsening of symptoms in the evening and night. This is often genetic but may also occur in the setting of iron deficiency, uremia, pregnancy, neuropathy, and possibly other conditions. The pathology is probably related to central nervous system iron dysregulation. Effective treatments include dopaminergics and narcotics. Recent advances in our understanding of RLS clinical presentation, epidemiology, etiology, and treatment will be discussed.

Adult↗