Objective assessment of the effects of opicapone in Parkinson's disease through kinematic analysis.

BACKGROUND: Opicapone (OPC) is a third-generation, selective peripheral COMT inhibitor that improves peripheral L-DOPA bioavailability and reduces OFF time and end-of-dose motor fluctuations in Parkinson's disease (PD) patients. OBJECTIVES: In this study, we objectively assessed the effects of adding OPC to L-DOPA on bradykinesia in PD through kinematic analysis of finger movements. METHODS: We enrolled 20 treated patients with PD and motor fluctuations. Patients underwent two experimental sessions (L-DOPA, L-DOPA + OPC), separated by at least 1 week. In each session, patients were clinically evaluated and underwent kinematic movement analysis of repetitive finger movements at four time points: (i) before their usual morning dose of L-DOPA (T0), (ii) 30 min (T1), (iii) 1 h and 30 min (T2), and (iv) 3 h and 30 min after the L-DOPA intake (T3). RESULTS: Movement velocity and amplitude of finger movements were higher in PD patients during the session with OPC compared to the session without OPC at all the time points tested. Importantly, the variability of finger movement velocity and amplitude across T0-T3 was significantly lower in the L-DOPA + OPC than L-DOPA session. CONCLUSIONS: This study is the first objective assessment of the effects of adding OPC to L-DOPA on bradykinesia in patients with PD and motor fluctuations. OPC, in addition to the standard dopaminergic therapy, leads to significant improvements in bradykinesia during clinically relevant periods associated with peripheral L-DOPA dynamics, i.e., the OFF state in the morning, delayed-ON, and wearing-OFF periods.

[The efficacy analysis of neurosurgical robot-assisted DBS in the treatment of elderly Parkinson's disease].

Objective: To investigate the surgical efficacy of neurosurgery robot deep brain stimulation(DBS) in the treatment of elderly Parkinson's disease(PD). Methods: The clinical data of elderly patients (≥75 years) with PD who underwent neurosurgical robot-assisted DBS surgery in the Department of Neurosurgery of the General Hospital of Northern Theater Command from September 2016 to September 2022 were collected retrospectively. Operation time, electrode implantation duration, postoperative pneumocephalus volume, electrode implantation accuracy, the Tao's DBS surgery scale, perioperative complications were analyzed.The unified Parkinson's disease rating scales (UPDRS), UPDRS-Ⅲ, tremor, rigidity, bradykinesia, axial, Barthel Activities of Daily Living (ADL-Barthel), Levodopa Equivalent Daily Dose (LEDD), Montreal Cognitive Assessment (MoCA), Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) scores and mortality were assessed respectively before operation, 6, 12 and 24 months after operation and last follow-up. Results: A total of 25 elderly patients were enrolled, including 14 males and 11 females, aged(78.3±3.2) years. Nine patients had underlying diseases. Nine patients (36%) underwent bilateral Globus Pallidus pars Interna deep brain stimulation (GPi-DBS) and 16 patients (64%) underwent bilateral subthalamic nucleus deep brain stimulation (STN-DBS).The operation time was (1.56±0.19) hours, the electrode implantation duration was (1.01±0.19) hours, the pneumocephalus volume was 9.8(4.7, 23.3) cm3, and the electrode implantation accuracy was (0.84±0.24) mm, the Tao's DBS surgery scale was (80.2±6.2).The follow-up time [M(Q1, Q3)] was 57.3(27.9, 75.7) months. No serious complications such as intracranial hemorrhage, infection or poor wound healing occurred during the perioperative period. The improvement rate of UPDRS, UPDRS-Ⅲ, rigidity, bradykinesia, and LEDD at 6 months after surgery was significantly higher than that at 24 months after surgery and at the last follow-up (all P<0.05); the improvement rate of axial symptoms, ADL-Barthel score, and MoCA score at 6 months after surgery was significantly higher than that at the last follow-up (P<0.05). HAMD and HAMA scores showed no significant improvement during follow-up after surgery (both P>0.05). At the last follow-up, 12 patients died, with death time of (35.1±20.2) months after operation, and the death age of [M(Q1, Q3)] 80(79, 83)years. Conclusions: Robot-assisted DBS surgery for elderly patients with PD is accurate and safe, and the postoperative symptoms are significantly improved, and they can benefit from neuromodulation for long term, and the risks are controllable.

[Clinical and genetic characteristics of children with dopa-responsive dystonia caused by tyrosine hydroxylase gene variations].

Objective: To explore the clinical and genetic characteristics of children with dopa-responsive dystonia (DRD) caused by tyrosine hydroxylase (TH) gene variations. Methods: Clinical data of 9 children with DRD caused by TH gene variations diagnosed in the Department of Children Rehabilitation, the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2022 were retrospectively collected and analyzed, including the general conditions, clinical manifestations, laboratory tests, gene variations and follow-up data. Results: Of the 9 children with DRD caused by TH gene variations, 3 were males and 6 were females. The age at diagnosis was 12.0 (8.0, 15.0) months. The initial symptoms of the 8 severe patients were motor delay or degression. Clinical symptoms of the severe patients included motor delay (8 cases), truncal hypotonia (8 cases), limb muscle hypotonia (7 cases), hypokinesia (6 cases), decreased facial expression (4 cases), tremor (3 cases), limb dystonia (3 cases), diurnal fluctuation (2 cases), ptosis (2 cases), limb muscle hypertonia (1 case) and drooling (1 case). The initial symptom of the very severe patient was motor delay. Clinical symptoms of the very severe patient included motor delay, truncal hypotonia, oculogyric crises, status dystonicus, hypokinesia, decreased facial expression, and decreased sleep. Eleven TH gene variants were found, including 5 missense variants, 3 splice site variants, 2 nonsense variants, and 1 insertion variant, as well as 2 novel variants (c.941C>A (p.T314K), c.316_317insCGT (p.F106delinsSF)). Nine patients were followed up for 40 (29, 43) months, and no one was lost to follow-up. Seven of the 8 severe patients were treated by levodopa and benserazide hydrochloride tablets and 1 severe patient was treated by levodopa tablets. All the severe patients responded well to levodopa and benserazide hydrochloride tablets or levodopa tablets. Although the weight of the patients increased and the drug dosage was not increased, the curative effect remained stable and there was no obvious adverse reaction. One severe patient developed dyskinesia in the early stage of treatment with levodopa and benserazide hydrochloride tablets and it disappeared after oral administration of benzhexol hydrochloride tablets. Until the last follow-up, motor development of 7 severe patients returned to normal and 1 severe patient still had motor delay due to receiving levodopa and benserazide hydrochloride tablets for only 2 months. The very severe patient was extremely sensitive to levodopa and benserazide hydrochloride tablets and no improvement was observed in this patient. Conclusions: Most of the DRD caused by TH gene variations are severe form. The clinical manifestations are varied and easily misdiagnosed. Patients of the severe patients responded well to levodopa and benserazide hydrochloride tablets or levodopa tablets, and it takes a long time before full effects of treatment become established. Long-term effect is stable without increasing the drug dosage, and no obvious side effect is observed.

Prolactin-Raising and Prolactin-Sparing Antipsychotic Drugs and the Risk of Fracture and Fragility Fracture in Patients With Schizophrenia, Dementia, and Other Disorders.

Patients who require antipsychotic drug treatment are at increased risk of fractures, including osteoporosis-related fragility fractures, for reasons related to demographics, illness-related factors, and treatment-related factors. As examples, patients with dementia may be vulnerable to falls due to cognitive and psychomotor impairment, patients with schizophrenia may be vulnerable to injury related to physical restlessness or physical aggression, and patients receiving antipsychotics may suffer falls related to sedation, psychomotor impairment, bradykinesia, or postural hypotension. Antipsychotics may also increase the risk of fracture through long-term hyperprolactinemia and resultant osteoporosis. A meta-analysis of 36 observational studies conducted in mostly elderly samples found that antipsychotic exposure was associated with an increased risk of hip fracture as well as increased risk of any fracture; the findings were consistent in almost all subgroup analyses. An observational study that controlled for confounding by indication and illness severity found that fragility fractures in patients with schizophrenia were associated with higher daily doses, higher cumulative doses, longer duration of treatment, and prolactin-raising rather than prolactin-sparing antipsychotics; in patients receiving prolactin-raising antipsychotics, the concurrent use of aripiprazole appeared protective. The absolute risks of fracture are unknown and could vary depending on patient age, patient sex, indication for antipsychotic use, nature of the antipsychotic (and associated risk of sedation, psychomotor impairment, bradykinesia, and postural hypotension), daily dose prescribed, duration of antipsychotic exposure, baseline risk of fracture, and other risk factors. Patients should therefore be individually evaluated for risk factors for falls and fractures related to sociodemographic, clinical, and treatment-related risk factors. Patients identified to be at risk should be advised about risk-mitigating strategies. If prolactin-raising antipsychotics are required in the long term, prolactin levels should be monitored and prolactin-lowering strategies should be considered. Osteoporosis should be investigated and managed, if identified, to prevent fragility fractures.

Levodopa Response in Patients With Early Parkinson Disease: Further Observations of the LEAP Study.

BACKGROUND AND OBJECTIVES: The Levodopa in EArly Parkinson's Disease (LEAP) study enabled us to conduct post hoc analyses concerning the effects of levodopa in patients with early Parkinson disease. METHODS: The LEAP study was a double-blind, placebo-controlled, randomized, delayed-start trial in which patients with early Parkinson disease were randomized to receive levodopa/carbidopa 300/75 mg daily for 80 weeks (early-start group) or to placebo for 40 weeks followed by levodopa/carbidopa 300/75 mg daily for 40 weeks (delayed-start group). We analyzed the effect of levodopa with the Unified Parkinson's Disease Rating Scale on bradykinesia, rigidity, and tremor. At week 80, participants answered 3 questions regarding motor response fluctuations. RESULTS: A total of 222 patients were randomized to the early-start group (mean ± SD age at baseline 64.8 ± 8.7 years; 71% male) and 223 to the delayed-start group (mean ± SD age at baseline 65.5 ± 8.8 years; 69% male). The difference between the early- and delayed-start groups in mean change from baseline to week 4, expressed as Hedges g effect size, was -0.33 for bradykinesia, -0.29 for rigidity, and -0.25 for tremor (for all symptoms indicating a small effect in favor of the early-start group); from baseline to week 22, respectively, -0.49, -0.36, and -0.44 (small to medium effect); and from baseline to week 40, respectively, -0.32, -0.19, and -0.27 (small effect). At 80 weeks, fewer patients in the early-start group (46 of 205 patients, 23%) experienced motor response fluctuations than patients in the delayed-start group (81 of 211, 38%; p < 0.01). DISCUSSION: In patients with early Parkinson disease, levodopa improves bradykinesia, rigidity, and tremor to the same order of magnitude. For all 3 symptoms, effects were larger at 22 weeks compared with 4 weeks. At 80 weeks, there were fewer patients with motor response fluctuations in the group that had started levodopa earlier. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that the effect of levodopa on bradykinesia, rigidity, and tremor is larger after 22 weeks compared with 4 weeks of treatment. TRIAL REGISTRATION INFORMATION: ISRCTN30518857, EudraCT number 2011-000678-72.

Clinical and genetic characteristics of children with dopa-responsive dystonia caused by tyrosine hydroxylase gene variations / 中华儿科杂志

Objective: To explore the clinical and genetic characteristics of children with dopa-responsive dystonia (DRD) caused by tyrosine hydroxylase (TH) gene variations. Methods: Clinical data of 9 children with DRD caused by TH gene variations diagnosed in the Department of Children Rehabilitation, the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2022 were retrospectively collected and analyzed, including the general conditions, clinical manifestations, laboratory tests, gene variations and follow-up data. Results: Of the 9 children with DRD caused by TH gene variations, 3 were males and 6 were females. The age at diagnosis was 12.0 (8.0, 15.0) months. The initial symptoms of the 8 severe patients were motor delay or degression. Clinical symptoms of the severe patients included motor delay (8 cases), truncal hypotonia (8 cases), limb muscle hypotonia (7 cases), hypokinesia (6 cases), decreased facial expression (4 cases), tremor (3 cases), limb dystonia (3 cases), diurnal fluctuation (2 cases), ptosis (2 cases), limb muscle hypertonia (1 case) and drooling (1 case). The initial symptom of the very severe patient was motor delay. Clinical symptoms of the very severe patient included motor delay, truncal hypotonia, oculogyric crises, status dystonicus, hypokinesia, decreased facial expression, and decreased sleep. Eleven TH gene variants were found, including 5 missense variants, 3 splice site variants, 2 nonsense variants, and 1 insertion variant, as well as 2 novel variants (c.941C>A (p.T314K), c.316_317insCGT (p.F106delinsSF)). Nine patients were followed up for 40 (29, 43) months, and no one was lost to follow-up. Seven of the 8 severe patients were treated by levodopa and benserazide hydrochloride tablets and 1 severe patient was treated by levodopa tablets. All the severe patients responded well to levodopa and benserazide hydrochloride tablets or levodopa tablets. Although the weight of the patients increased and the drug dosage was not increased, the curative effect remained stable and there was no obvious adverse reaction. One severe patient developed dyskinesia in the early stage of treatment with levodopa and benserazide hydrochloride tablets and it disappeared after oral administration of benzhexol hydrochloride tablets. Until the last follow-up, motor development of 7 severe patients returned to normal and 1 severe patient still had motor delay due to receiving levodopa and benserazide hydrochloride tablets for only 2 months. The very severe patient was extremely sensitive to levodopa and benserazide hydrochloride tablets and no improvement was observed in this patient. Conclusions: Most of the DRD caused by TH gene variations are severe form. The clinical manifestations are varied and easily misdiagnosed. Patients of the severe patients responded well to levodopa and benserazide hydrochloride tablets or levodopa tablets, and it takes a long time before full effects of treatment become established. Long-term effect is stable without increasing the drug dosage, and no obvious side effect is observed.

Rapid Dynamic Naturalistic Monitoring of Bradykinesia in Parkinson's Disease Using a Wrist-Worn Accelerometer.

Motor fluctuations in Parkinson's disease are characterized by unpredictability in the timing and duration of dopaminergic therapeutic benefits on symptoms, including bradykinesia and rigidity. These fluctuations significantly impair the quality of life of many Parkinson's patients. However, current clinical evaluation tools are not designed for the continuous, naturalistic (real-world) symptom monitoring needed to optimize clinical therapy to treat fluctuations. Although commercially available wearable motor monitoring, used over multiple days, can augment neurological decision making, the feasibility of rapid and dynamic detection of motor fluctuations is unclear. So far, applied wearable monitoring algorithms are trained on group data. In this study, we investigated the influence of individual model training on short timescale classification of naturalistic bradykinesia fluctuations in Parkinson's patients using a single-wrist accelerometer. As part of the Parkinson@Home study protocol, 20 Parkinson patients were recorded with bilateral wrist accelerometers for a one hour OFF medication session and a one hour ON medication session during unconstrained activities in their own homes. Kinematic metrics were extracted from the accelerometer data from the bodyside with the largest unilateral bradykinesia fluctuations across medication states. The kinematic accelerometer features were compared over the 1 h duration of recording, and medication-state classification analyses were performed on 1 min segments of data. Then, we analyzed the influence of individual versus group model training, data window length, and total number of training patients included in group model training, on classification. Statistically significant areas under the curves (AUCs) for medication induced bradykinesia fluctuation classification were seen in 85% of the Parkinson patients at the single minute timescale using the group models. Individually trained models performed at the same level as the group trained models (mean AUC both 0.70, standard deviation respectively 0.18 and 0.10) despite the small individual training dataset. AUCs of the group models improved as the length of the feature windows was increased to 300 s, and with additional training patient datasets. We were able to show that medication-induced fluctuations in bradykinesia can be classified using wrist-worn accelerometry at the time scale of a single minute. Rapid, naturalistic Parkinson motor monitoring has the clinical potential to evaluate dynamic symptomatic and therapeutic fluctuations and help tailor treatments on a fast timescale.

Comparison of the Parkinson's KinetiGraph to off/on levodopa response testing: Single center experience.

BACKGROUND AND OBJECTIVE: Levodopa off/on testing is frequently performed to assess medication response in patients with Parkinson's disease (PD) as an aid in determining best medical management or potential surgical candidacy. The Parkinson's Kinetigraph (PKG) is a wearable device which generates tremor, bradykinesia (BKS) and dyskinesia (DKS) scores representing motor symptoms over a six-day period. In this study, we compared off/on testing with PKG motor scores. METHODS: Patients were enrolled as part of an observational study: Assessing the Longitudinal Signs in PD, a three-year study evaluating clinical and biomarker evolution in patients with PD taking levodopa. Patients underwent off/on testing at baseline and 6-month visits. A greater than 30% improvement between off and on MDS-Unified Parkinson's Disease Rating Scale scores was considered a robust response. After each visit, patients wore the PKG for 6 days. A bradykinesia score (BKS) greater than 26 and dyskinesia score (DKS) greater than 9 were considered poorly controlled bradykinesia and dyskinesia, respectively. RESULTS: The median BKS at the baseline and 6-month visits were 27.15 and 27.55, respectively, despite a robust median off/on improvement at both visits. In addition, 10/18 (66%) and 7/13 (53.8%) patients with robust off/on improvement at the baseline and 6-month visits, respectively, demonstrated a BKS > 26 or DKS > 9. CONCLUSION: A robust off/on response during a clinic visit does not necessarily reflect adequately controlled motor symptoms. The PKG, by virtue of its continuous recording of motor movements, may provide additional clinically relevant data on motor symptoms which may be useful for prospective observational studies.

Comparing subjective and objective response to medications in Parkinson's disease patients using the Personal KinetiGraph™.

BACKGROUND: Management of motor symptoms in Parkinson's Disease(PD) relies on subjective information provided by patients, the quality of which can be affected by many factors. RATIONALE: Objective data collected during daily life could complement this information and improve management of motor symptoms. OBJECTIVES: To assess the usefulness of the Personal KinetiGraph (PKG) in characterizing the intensity and timing of motor symptoms in PD patients. METHODS: Retrospective study of all PD patients followed at a tertiary academic movement disorders center assessed by PKG between December 1, 2016 and October 30, 2018. PKG was worn for 7 days prior to the clinical visit. We compared the information obtained from the interview and the clinical visit, and assessed the impact of the PKG on treatment decision making. RESULTS: 170 PKG results were reviewed. PKG complemented patient input in 82.9%(141/170) and led to medication changes in 71%(100/141) of the complemented inputs. PKG contributed the least to correcting or complementing patients' input when patients self-reported as undertreated (22%) and the most when patient were unable to answer all questions regarding motor response to individual doses (100%) (Fisher, p < 0.0001). The majority of patient undergoing 3 or 4 PKG encounters did not reach a controlled state as defined by PKG until the 3rd or 4th encounter, suggesting that repeated use of the PKG might be needed to help optimize motor control as therapy changes done after one encounter might not be enough. CONCLUSIONS: PKG might be useful in supplementing patient-provided information for accurate assessment and treatment plan.

Effect of Anti-Glutamate Antibodies in Modeled Parkinsonian Syndrome.

We studied the effect of single and repeated intranasal administration of antibodies to glutamate in experimental parkinsonian syndrome induced by injections of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to C57BL/6J mice. Intranasal administration of anti-glutamate antibodies to mice in parallel with administration of MPTP over 10 days alleviated parkinsonian symptoms (oligokinesia and rigidity). In the serum of mice injected with antibodies to glutamate and/or MPTP, the titers of autoantibodies to glutamate and dopamine were higher than in control animals receiving saline. Single intranasal administration of anti-glutamate antibodies to mice with established parkinsonian syndrome did not affect the severity of parkinsonian symptoms.

Dopamine-responsive and dopamine-resistant resting tremor in Parkinson disease.

OBJECTIVE: We tested the hypothesis that there are 2 distinct phenotypes of Parkinson tremor, based on interindividual differences in the response of resting tremor to dopaminergic medication. We also investigated whether this pattern is specific to tremor by comparing interindividual differences in the dopamine response of tremor to that of bradykinesia. METHODS: In this exploratory study, we performed a levodopa challenge in 76 tremulous patients with Parkinson tremor. Clinical scores (Movement Disorders Society-sponsored version of the Unified Parkinson's Disease Rating Scale part III) were collected "off" and "on" a standardized dopaminergic challenge (200/50 mg dispersible levodopa-benserazide). In both sessions, resting tremor intensity was quantified using accelerometry, both during rest and during cognitive coactivation. Bradykinesia was quantified using a speeded keyboard test. We calculated the distribution of dopamine-responsiveness for resting tremor and bradykinesia. In 41 patients, a double-blinded, placebo-controlled dopaminergic challenge was repeated after approximately 6 months. RESULTS: The dopamine response of resting tremor, but not bradykinesia, significantly departed from a normal distribution. A cluster analysis on 3 clinical and electrophysiologic markers of tremor dopamine-responsiveness revealed 3 clusters: dopamine-responsive, intermediate, and dopamine-resistant tremor. A repeated levodopa challenge after 6 months confirmed this classification. Patients with dopamine-responsive tremor had greater disease severity and tended to have a higher prevalence of dyskinesia. CONCLUSION: Parkinson resting tremor can be divided into 3 partially overlapping phenotypes, based on the dopamine response. These tremor phenotypes may be associated with different underlying pathophysiologic mechanisms, requiring a different therapeutic approach.

Peculiarities of Pharmacokinetics and Bioavailability of Some Cardiovascular Drugs under Conditions of Antiorthostatic Hypokinesia.

We studied pharmacokinetics and bioavailability of verapamil, propranolol, and ethacizine in healthy volunteers after single oral administration under normal conditions and on the second day of simulated antiorthostatic hypokinesia modeling some effects of microgravity. Under conditions of antiorthostatic hypokinesia, a tendency to a decrease in half-elimination period, mean retention time, and volume of distribution and an increase in the rate of absorption, ratio of maximum concentrations, and relative rate of absorption of verapamil and propranolol were revealed. For ethacizine, a statistically significant increase in the time of attaining maximum concentration and volume of distribution and a decrease in the maximum concentration, rate of absorption, ratio of maximum concentrations, and relative rate of absorption under conditions of antiorthostatic hypokinesia were found.

Evolving concepts on bradykinesia.

Bradykinesia is one of the cardinal motor symptoms of Parkinson's disease and other parkinsonisms. The various clinical aspects related to bradykinesia and the pathophysiological mechanisms underlying bradykinesia are, however, still unclear. In this article, we review clinical and experimental studies on bradykinesia performed in patients with Parkinson's disease and atypical parkinsonism. We also review studies on animal experiments dealing with pathophysiological aspects of the parkinsonian state. In Parkinson's disease, bradykinesia is characterized by slowness, the reduced amplitude of movement, and sequence effect. These features are also present in atypical parkinsonisms, but the sequence effect is not common. Levodopa therapy improves bradykinesia, but treatment variably affects the bradykinesia features and does not significantly modify the sequence effect. Findings from animal and patients demonstrate the role of the basal ganglia and other interconnected structures, such as the primary motor cortex and cerebellum, as well as the contribution of abnormal sensorimotor processing. Bradykinesia should be interpreted as arising from network dysfunction. A better understanding of bradykinesia pathophysiology will serve as the new starting point for clinical and experimental purposes.

Fact-finding survey on diagnostic procedures and therapeutic interventions for parkinsonism accompanying dementia with Lewy bodies.

BACKGROUND: We performed a questionnaire survey of medical doctors engaged in the management of dementia to identify the actual status of treatment for dementia with Lewy bodies (DLB) in Japan. METHODS: Among participating medical doctors, we selected neurologists (Group N) and psychiatrists (Group P) because these physicians are usually involved in the management of DLB patients. The two groups were compared based on their diagnosis and treatment of DLB and in particular, parkinsonism. RESULTS: Neurological examinations and biomarker tests were less frequently performed by Group P than Group N. Antipsychotics and other psychotropics excluding anti-dementia drugs were significantly more frequently administered by Group P than Group N. The proportion of physicians who selected L-dopa as a first-line therapy for parkinsonism was significantly higher in Group N than in Group P. Despite these between-group differences, the following findings were common to the two groups: there was a discrepancy between the symptom that patients expressed the greatest desire to treat, and the awareness of physicians regarding the treatment of these symptoms; the initial agent was L-dopa; and physicians exercised caution against the occurrence of hallucinations, delusions, and other adverse drug reactions. CONCLUSIONS: The results of the present survey offer valuable insight for the formulation of future DLB therapeutic strategies.

Reversible Non-parkinsonian Bradykinesia with Impaired Frontal Lobe Function as the Predominant Manifestation of Adrenal Insufficiency.

A 69-year-old Japanese man with a history of suprasellar surgery and irradiation developed bradykinesia and mild fatigue without muscle weakness, myalgia, pyramidal or extrapyramidal signs, parkinsonian symptoms, or ataxia. An endocrinological work-up revealed anterior hypopituitarism associated with secondary adrenal insufficiency. Higher brain function tests indicated an impaired frontal lobe function. The patient's bradykinesia, fatigue, and frontal lobe dysfunction improved within 2 weeks after the initiation of corticosteroid replacement therapy. To our knowledge, this is the first reported case of adrenal insufficiency manifesting as non-parkinsonian bradykinesia. Physicians should consider reversible non-parkinsonian bradykinesia associated with frontal lobe dysfunction as an unusual manifestation of adrenal insufficiency.

Motor asymmetry over time in Parkinson's disease.

BACKGROUND: Motor symptoms in Parkinson's disease (PD) patients are usually asymmetric at onset. The literature on change in asymmetry over time has mixed results, with some studies suggesting a retained asymmetry and others suggesting a progression towards symmetry. The aim of this study was to assess change in asymmetry over time. METHODS: Charts of 109 consecutive patients who had been followed in a movement disorders clinic for routine PD care were retrospectively reviewed. All patients had been treated for PD symptoms and had been seen during at least 2 annual time points over 5 years. Interval absolute differences in Unified PD rating scale (UPDRS) scores for bradykinesia, rigidity, and tremor between the right and left sides were calculated for annual time points. RESULTS: Neither bradykinesia, rigidity, nor tremor became more symmetric over a 5-year period; there was not a statistically significant change in asymmetry at any annual time point for these motor symptoms. CONCLUSIONS: The lack of observed change in UPDRS score difference suggests that motor symptoms in PD patients remain asymmetric. This is important to consider clinically when predicting the natural course of PD and considering alternative diagnoses to PD. These results may also be important in developing hypotheses for disease progression.

Aberrant learning in Parkinson's disease: A neurocomputational study on bradykinesia.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by a progressive decline in motor functions, such as bradykinesia, caused by the pathological denervation of nigrostriatal dopaminergic neurons within the basal ganglia (BG). It is acknowledged that dopamine (DA) directly affects the modulatory role of BG towards the cortex. However, a growing body of literature is suggesting that DA-induced aberrant synaptic plasticity could play a role in the core symptoms of PD, thus recalling for a "reconceptualization" of the pathophysiology. The aim of this work was to investigate DA-driven aberrant learning as a concurrent cause of bradykinesia, using a comprehensive, biologically inspired neurocomputational model of action selection in the BG. The model includes the three main pathways operating in the BG circuitry, that is the direct, indirect and hyperdirect pathways, and use a two-term Hebb rule to train synapses in the striatum, based on previous history of rewards and punishments. Levodopa pharmacodynamics is also incorporated. Through model simulations of the Alternate Finger Tapping motor task, we assessed the role of aberrant learning on bradykinesia. The results show that training under drug medication (levodopa) provides not only immediate but also delayed benefit lasting in time. Conversely, if performed in conditions of vanishing levodopa efficacy, training may result in dysfunctional corticostriatal synaptic plasticity, further worsening motor performances in PD subjects. This suggests that bradykinesia may result from the concurrent effects of low DA levels and dysfunctional plasticity and that training can be exploited in medicated subjects to improve levodopa treatment.

Rotigotine for nocturnal hypokinesia in Parkinson's disease: Quantitative analysis of efficacy from a randomized, placebo-controlled trial using an axial inertial sensor.

BACKGROUND: Nocturnal hypokinesia is a common symptom in Parkinson's disease (PD), negatively affecting quality of life of both patients and caregivers. However, evidence-based treatment strategies are limited. OBJECTIVE: To evaluate the efficacy of rotigotine transdermal patch, using a wearable sensor, in the management of nocturnal immobility. METHODS: 34 PD subjects with nocturnal immobility were randomized to receive rotigotine transdermal patch (mean ± SD of 10.46 ± 4.63 mg/24 h, n = 17) or placebo patch (n = 17). Treatment was titrated to an optimal dose over 1-8 weeks, then maintained for 4 weeks. Primary endpoints were objective parameters assessing axial rotation measured using an axial inertial sensor (the NIGHT-Recorder) over two nights at the patients' home. Scale-based assessments were also performed. RESULTS: There was a significant difference, in favor of rotigotine, in change from baseline score in the number of turns in bed (ANCOVA, p = 0.001), and degree of axial turn (p = 0.042). These objective improvements were mirrored by significantly greater improvements in clinical scale-based assessments, including the Unified Parkinson's Disease Rating Scale (UPDRS) total scores (p = 0.009), UPDRS-motor scores (p < 0.001), UPDRS-axial scores (p = 0.01), the Modified Parkinson's Disease Sleep Scale (p < 0.001), the Nocturnal Akinesia Dystonia and Cramp Scale (p = 0.003) and the eight-item PD Questionnaire (PDQ-8) scores (p = 0.01) from baseline to end of treatment in patients given rotigotine compared to placebo. CONCLUSION: We show that the rotigotine patch provides a significant improvement in nocturnal symptoms as assessed using both objective measures and clinical rating scales. The study demonstrates the feasibility of using wearable sensors to record objective outcomes in PD-related clinical trials.

Eradication of Helicobacter pylori infection might improve clinical status of patients with Parkinson's disease, especially on bradykinesia.

OBJECTIVES: Previous studies have shown that Helicobacter pylori infection might make clinical status worse in patients with Parkinson's disease and Helicobacter pylori eradication might improve clinical status by modifying the pharmacokinetics of L-dopa. Here, we investigate whether Helicobacter pylori eradication could benefit idiopathic parkinsonism and Helicobacter pylori infection will effect which aspect of motor symptom significantly. PATIENTS AND METHODS: A cohort study involving idiopathic Parkinson's disease patients, screened for Helicobacter status by 13C urea breath test. Clinical status was evaluated by using the Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn-Yahr stage. If patients had motor complications, they were quantified at the "on" time. The Helicobacter pylori positive patients could choose to receive Helicobacter pylori eradication or not by themselves. Group 1 was Helicobacter pylori negative patients. Group 2 was Helicobacter pylori positive patients who didn't receive eradication treatment. Group 3 was Helicobacter pylori positive patients who received successful eradication treatment. Repeat clinical assessments and 13C urea breath test was performed at 1year later. Numerical data were expressed as mean±standard deviation (SD) RESULTS: Ninety-four consecutive patients with Parkinson's disease were recruited and underwent the initial 13C urea breath test, but only forty-eight patients successfully completed the total study. In Group 3, the UPDRS-III scores (=Motor Examination Section Scores) were significantly lower 1year later compared to baseline (18.3±8.38 vs. 25.9±8.37, P=0.007). The differences were main in UPDRS-23 (=Finger Taps) (1.7±1.16 vs. 2.4±1.51, P=0.045), UPDRS-25 (Rapid Alternation Movements of Hands) (1.6±1.35 vs. 2.4±1.71, P=0.031) and UPDRS-26 (=Leg Agility) (1.3±1.25 vs.2.1±0.99, P=0.011). There was difference among three groups in the UPDRS-26 (P=0.040) of clinical status change of one year. CONCLUSION: The eradication of Helicobacter might improve the clinical status of idiopathic parkinsonism, especially on bradykinesia.