Medical Devices for Tremor Suppression: Current Status and Future Directions.

Tremors are the most prevalent movement disorder that interferes with the patient's daily living, and physical activities, ultimately leading to a reduced quality of life. Due to the pathophysiology of tremor, developing effective pharmacotherapies, which are only suboptimal in the management of tremor, has many challenges. Thus, a range of therapies are necessary in managing this progressive, aging-associated disorder. Surgical interventions such as deep brain stimulation are able to provide durable tremor control. However, due to high costs, patient and practitioner preference, and perceived high risks, their utilization is minimized. Medical devices are placed in a unique position to bridge this gap between lifestyle interventions, pharmacotherapies, and surgical treatments to provide safe and effective tremor suppression. Herein, we review the mechanisms of action, safety and efficacy profiles, and clinical applications of different medical devices that are currently available or have been previously investigated for tremor suppression. These devices are primarily noninvasive, which can be a beneficial addition to the patient's existing pharmacotherapy and/or lifestyle intervention.

Patient selected goals and satisfaction after bilateral subthalamic nucleus deep brain stimulation in Parkinson's disease.

Assessing patient goals is crucial in understanding patient centered outcomes and satisfaction. However, patient goals may change throughout treatment. Our objective is to identify the changes in patient-selected goals of Parkinson's disease (PD) patients undergoing bilateral subthalamic nucleus deep brain stimulation (STN-DBS) and examine the relationship among patient-selected goal achievement, standard DBS outcome measures, and overall patient satisfaction. Seventy-five patients undergoing bilateral STN-DBS listed three patient-selected goals before surgery. After six months, patients were asked to restate the three goals and to rate the degree of goal achievement and the overall satisfaction of surgery. The three most frequently selected goals were "dyskinesia", "gait disorder", and "medication off duration". After six months, 80.0% of patients could not accurately recall their pre-DBS goals. "Dyskinesia" was the most consistently selected goal, more patients selected "tremor" and "less medication" at post-DBS compared to pre-DBS, and less patients selected "gait disorder" at post-DBS compared to pre-DBS. 74.7% of patients reported overall satisfaction by stating they were "very much" or "much better after surgery". Patient satisfaction significantly correlated with goal achievement (r = 0.640; p < 0.001). Interestingly, change in UPDRS motor scores did not correlate with patient satisfaction (r = 0.100; p = 0.395). Although recalled goals do not accurately represent the pre-surgical goals, the achievement score for recalled goals significantly correlated with patient satisfaction. Patient goals change due to many reasons. Therefore, follow-up patient counseling to discuss goals and outcomes is important in improving patient satisfaction after STN-DBS.

Purkinje cell misfiring generates high-amplitude action tremors that are corrected by cerebellar deep brain stimulation.

Tremor is currently ranked as the most common movement disorder. The brain regions and neural signals that initiate the debilitating shakiness of different body parts remain unclear. Here, we found that genetically silencing cerebellar Purkinje cell output blocked tremor in mice that were given the tremorgenic drug harmaline. We show in awake behaving mice that the onset of tremor is coincident with rhythmic Purkinje cell firing, which alters the activity of their target cerebellar nuclei cells. We mimic the tremorgenic action of the drug with optogenetics and present evidence that highly patterned Purkinje cell activity drives a powerful tremor in otherwise normal mice. Modulating the altered activity with deep brain stimulation directed to the Purkinje cell output in the cerebellar nuclei reduced tremor in freely moving mice. Together, the data implicate Purkinje cell connectivity as a neural substrate for tremor and a gateway for signals that mediate the disease.

Mechanical vibration does not systematically reduce the tremor in essential tremor patients.

Essential tremor (ET) is a major cause of disability and is not effectively managed in half of the patients. We investigated whether mechanical vibration could reduce tremor in ET by selectively recruiting afferent pathways. We used piezoelectric actuators to deliver vibratory stimuli to the hand and forearm during long trials (4 min), while we monitored the tremor using inertial sensors. We analyzed the effect of four stimulation strategies, including different constant and variable vibration frequencies, in 18 ET patients. Although there was not a clear homogeneous response to vibration across patients and strategies, in most cases (50-72%) mechanical vibration was associated with an increase in the amplitude of their tremor. In contrast, the tremor was reduced in 5-22% of the patients, depending on the strategy. However, these results are hard to interpret given the intrinsic variability of the tremor: during equally long trials without vibration, the tremor changed significantly in 67% of the patients (increased in 45%; decreased in 22%). We conclude that mechanical vibration of the limb does not have a systematic effect on tremor in ET. Moreover, the observed intrinsic variability of the tremor should be taken into account when designing future experiments to assess tremor in ET and how it responds to any intervention.

Treatment with potassium bromide mitigates ataxia and reduces tremor in lambs with perennial ryegrass toxicosis.

Aims: To assess the use of potassium bromide (KBr) as a therapeutic intervention for perennial ryegrass toxicosis (PRGT) in lambs fed ryegrass seed containing lolitrem B. Methods: Male lambs aged 10-12 months (n = 43) were assigned to receive ryegrass seed containing lolitrem B, at a dose of 0.16 mg/kg/day (Groups 2, 3 and 4), or lucerne chaff and molasses (Groups 1 and 5). Lambs in Groups 2 and 3 were observed for clinical signs and gait changes until defined signs of PGRT were observed, when they were transferred, with lambs in Group 1, to the Testing phase of the trial. Lambs in Group 3 were then treated with a single oral dose of 300 mg/kg bromide. Lambs in Groups 4 and 5 received KBr daily from the start of the trial (540 mg/kg bromide over 3 days then 20 mg/kg daily) and were transferred to the Testing phase after 18 days. Clinical examination and gait assessment, and surface electromyography of the triceps muscle, measuring root-mean-square (RMS) voltages, were carried out on Days 0, 1 and 2 of the Testing phase followed by necropsy, histopathology, measurement of concentrations of bromide in serum and CSF and faecal cortisol metabolites (FCM). Results: In Group 3 lambs, mean composite gait scores decreased between Testing phase Day 0 and Days 1 and 2 (p < 0.001), but increased in lambs in Group 2 between Day 0 and Day 2 (p = 0.015). Scores for lambs in Group 3 on Day 2 were lower than for lambs in Group 2 (p < 0.001). Mean RMS voltages on Day 2 were higher in lambs in Group 2 than Group 3 (p = 0.045). Mean concentrations of bromide in serum were >800 µg/mL in lambs in Groups 3 and 4 on Day 2. Concentrations of FCM were higher in lambs from Group 2 than in Groups 1 or 5, but were similar in Groups 2, 3 and 4. Histopathological findings in the cerebellum of lambs from Groups 2, 3 and 4 were similar, showing pyknosis of neurons within the granular layer of the cerebellum and Purkinje neuron proximal axonal spheroid formation. Conclusions and clinical relevance: A single oral dose of 300 mg/kg bromide in lambs with neurological signs of PRGT resulted in reduced composite gait scores and reduced RMS voltages, indicating a significant improvement in clinical signs of ataxia, movement disorder and muscle tremor associated with the neurotoxic effects of lolitrem B.

Robot-assisted tremor control for performance enhancement of retinal microsurgeons.

Pars plana vitrectomy is a challenging, minimally invasive microsurgical procedure due to its intrinsic manoeuvres and physiological limits that constrain human capability. An important human limitation is physiological hand tremor, which can significantly increase the risk of iatrogenic retinal damage resulting from unintentional manoeuvres that affect anatomical and functional surgical outcomes. The limitations imposed by normal physiological tremor are more evident and challenging during 'micron-scale' manoeuvres such as epiretinal membrane and internal limiting membrane peeling, and delicate procedures requiring coordinated bimanual surgery such as tractional retinal detachment repair. Therefore, over the previous three decades, attention has turned to robot-assisted surgical devices to overcome these challenges. Several systems have been developed to improve microsurgical accuracy by cancelling hand tremor and facilitating faster, safer and more effective microsurgeries. By markedly reducing tremor, microsurgical precision is improved to a level beyond present human capabilities. In conclusion, robotics offers potential advantages over free-hand microsurgery as it is currently performed during ophthalmic surgery and opens the door to a new class of revolutionary microsurgical modalities. The skills transfer that is beyond human capabilities to robotic technology is a logical next step in microsurgical evolution.

Low-dose acute vanillin is beneficial against harmaline-induced tremors in rats.

OBJECTIVE: To study the effect of pretreatment with low doses of vanillin, a flavoring agent used as a food additive, on harmaline-induced tremor in rats. METHODS: Sprague Dawley rats (110 ± 5 g) were divided into groups of six animals each. Vanillin (6.25 mg, 12.5 mg, and 25 mg/kg) was administered by gavage to different groups of rats, 30 minutes before the induction of tremor. Harmaline (10 mg/kg, i.p.) was used for the induction of tremor. The latency of onset, duration, tremor intensity, tremor index, and spontaneous locomotor activity were recorded. A separate batch of animals was used for the determination of serotonin (5HT) and 5 hydroxyindole acetic acid (5HIAA) levels in the brain. RESULTS: Harmaline treatment resulted in characteristic tremor that lasted for more than 2 hours and decreased the locomotor activity of rats. Pre-treatment with vanillin significantly reduced the duration, intensity, and tremor index of harmaline-treated animals. Vanillin treatment also significantly attenuated harmaline-induced decrease in the locomotor activity. An increase in 5HT levels and the changes in 5HIAA/5HT ratio observed in harmaline treated rats were significantly corrected in vanillin pretreated animals. DISCUSSION: Vanillin in low doses reduces harmaline-induced tremor in rats, probably through its modulating effect on serotonin levels in the brain. These findings suggest a beneficial effect of vanillin in essential tremor.

Endoscope-Assisted Microsurgical Removal of an Intraventricular Ependymal Cyst That Manifested with Tremor.

BACKGROUND: Intraventricular ependymal cysts (ECs) are rare, histologically benign neuroepithelial cysts. Most of these cysts are clinically silent and discovered incidentally. Rarely, they become symptomatic, leading to obstruction of the cerebrospinal fluid circulation. ECs located inside the ventricles may manifest with signs of increased intracranial pressure. CASE DESCRIPTION: A 32-year-old woman presented with a 6-year history of tremor affecting her left hand. In the last month, she had been experiencing headache as well, and the tremor of the left hand was affecting her quality of life. The patient demonstrated a fine resting and intention tremor of the left hand and a voice tremor. Magnetic resonance imaging revealed a large cystic, nonenhancing lesion within the right lateral ventricle. The fluid within the cyst was isointense to cerebrospinal fluid on all sequences. Because of the rapid progression of her symptoms and no response to medication, surgical decompression of the cyst was considered. The cyst was removed by an endoscope-assisted microsurgical technique. Her postoperative course was uneventful. A marked reduction in her tremor was noted in the immediate postoperative period. Histopathologic diagnosis was of an EC. During the follow-up period, the patient's tremor, although still present, had improved dramatically. At 6 months postoperatively, she could hold a drinking glass without spilling. CONCLUSIONS: This is a unique case of an intraventricular EC that manifested with tremor, which improved by endoscope-assisted microsurgical removal of the cyst. This case also supports the important role of endoscopic surgery in the treatment of intraventricular cystic lesions.

[Tremor Suppression on Multi-DoF Wrist Joint Based on Functional Electrical Stimulation: A Simulation Study].

An automatic control system was designed to suppress pathological tremor on wrist joint with two degrees of freedom (DoF) using functional electrical stimulation (FES). The tremor occurring in the wrist flexion-extension and adduction-abduction was expected to be suppressed. A musculoskeletal model of wrist joint was developed to serve as the control plant, which covered four main muscles (extensor carpi radialis longus, extensor carpi ulnaris, flexor carpi radialis, and flexor carpi ulnaris). A second-order mechanical impedance model was used to describe the wrist skeletal dynamics. The core work was to design the controller and a hybrid control strategy was proposed, which combined inverse model based on feed forward control and linear quadratic regulator (LQR) optimal control. Performance of the system was tested under different input conditions (step signal, sinusoidal signal, and real data of a patient)., The results indicated that the proposed hybrid controller could attenuate over 94% of the tremor amplitude on multi-DoF wrist joint.

Switching STudy of Kidney TRansplant PAtients with Tremor to LCP-TacrO (STRATO): an open-label, multicenter, prospective phase 3b study.

Tremor is a common side effect of tacrolimus correlated with peak-dose drug concentration. LCPT, a novel, once-daily, extended-release formulation of tacrolimus, has a reduced Cmax with comparable AUC exposure, requiring a ~30% dose reduction vs. immediate-release tacrolimus. In this phase 3b study, kidney transplant recipients (KTR) on a stable dose of tacrolimus and with a reported clinically significant tremor were offered a switch to LCPT. Tremor pre- and seven d post-conversion was evaluated by independent, blinded movement disorder neurologists using the Fahn-Tolosa-Marin (FTM) scale and by an accelerometry device; patients completed the QUEST (quality of life in essential tremor) and the Patient Global Impression of Change. There were 38 patients in the mITT population. A statistically and clinically significant improvement in tremor (FTM score, amplitude as measured by the accelerometry device and QOL [p-values < 0.05]) resulted post-conversion. Change in QUEST was significantly (p = 0.006) correlated (R = 0.44) with change in FTM; 78.9% of patients reported an improvement after switching to LCPT (p < 0.0005). To our knowledge this is the first trial in KTR that utilizes a sophisticated and reproducible measurement of tremor. Results suggest LCPT is associated with clinically meaningful improvement of hand tremor and may be an alternative management approach in lieu of further dose reduction of immediate-release tacrolimus for patients experiencing tremor.

Hydroxycinnamic acid amide derivatives of polyamines reverse spermine-induced CNS excitation.

The aim of this study was to examine the acute effect of a range of novel hydroxycinnamic acid derivatives of spermine on the development of spermine-induced CNS excitation and convulsions in female Laca mice, and to assess the chronic adverse behavioural effect profile of these compounds over a 5day period. Four of the six novel polyamine analogues dose-dependently inhibited body tremor and tonic convulsions caused by spermine, when administered centrally (icv) or peripherally (ip). BU43b was the most potent analogue tested, but BU31b, 33b, and 36b were also effective (p<0.01, Mann-Whitney U test). A similar profile of effectiveness was seen with peripheral and central administration, indicating that the analogues may cross the blood brain barrier. More chronic investigation of the adverse effects of the compounds administered alone over 5days of observation indicated that the drugs were well tolerated, only causing reduced locomotor activity on the first day of the study and mild changes in behaviours linked to CNS and ANS function. It is likely that NMDA receptor NR2B subunit inhibition is involved in the anticonvulsant effect of these novel analogues, but other mechanisms may also be involved. These novel polyamine derivatives warrant further investigation of their therapeutic potential in treating epilepsy and CNS disorders where excitotoxicity is implicated.

An armrest is effective for reducing hand tremble in neurosurgeons.

Experienced neurosurgeons reduce hand tremble by placing their hand beside the operative field when performing microneurosurgery conventionally. Another solution to reduce hand tremble is an armrest. However, the reduction of hand tremble by using an armrest or finger-placing technique has not been rigorously measured in microneurosurgery. This study was performed to provide a quantitative assessment of the efficacy of an armrest to reduce hand tremble in comparison with the finger-placing technique. Hand tremble was evaluated in 11 board-certified neurosurgeons in a simulated microneurosurgery. The loci of surgical forceps handled by neurosurgeons were measured by a three-dimensional optical coordinate measuring machine. A static task was performed under four conditions: with/without the finger-placing technique and/or an armrest. The radius of an imaginative sphere including 95% of each locus was calculated and reviewed according to the four conditions. Hand tremble was significantly larger when the finger-placing technique was not implemented compared to when the technique was used (P<0.05). The armrest also reduced hand tremble (P<0.05) similar to the finger-placing technique. Non-inferiority was retained between the finger-placing technique and the armrest. Concomitant use of the armrest and the finger-placing technique did not interfere with the efficacy of the technique to reduce neurosurgeon's hand tremble. The finger-placing technique was confirmed to reduce hand tremble. Resting the neurosurgeon's forearm on an armrest also reduced the hand tremble. An armrest is a device that reduces hand tremble in neurosurgeons like the finger-placing technique.

Hand-held medical robots.

Medical robots have evolved from autonomous systems to tele-operated platforms and mechanically-grounded, cooperatively-controlled robots. Whilst these approaches have seen both commercial and clinical success, uptake of these robots remains moderate because of their high cost, large physical footprint and long setup times. More recently, researchers have moved toward developing hand-held robots that are completely ungrounded and manipulated by surgeons in free space, in a similar manner to how conventional instruments are handled. These devices provide specific functions that assist the surgeon in accomplishing tasks that are otherwise challenging with manual manipulation. Hand-held robots have the advantages of being compact and easily integrated into the normal surgical workflow since there is typically little or no setup time. Hand-held devices can also have a significantly reduced cost to healthcare providers as they do not necessitate the complex, multi degree-of-freedom linkages that grounded robots require. However, the development of such devices is faced with many technical challenges, including miniaturization, cost and sterility, control stability, inertial and gravity compensation and robust instrument tracking. This review presents the emerging technical trends in hand-held medical robots and future development opportunities for promoting their wider clinical uptake.

Effect of fluoxetine on disease progression in a mouse model of ALS.

Selective serotonin reuptake inhibitors (SSRIs) and other antidepressants are often prescribed to amyotrophic lateral sclerosis (ALS) patients; however, the impact of these prescriptions on ALS disease progression has not been systematically tested. To determine whether SSRIs impact disease progression, fluoxetine (Prozac, 5 or 10 mg/kg) was administered to mutant superoxide dismutase 1 (SOD1) mice during one of three age ranges: neonatal [postnatal day (P)5-11], adult presymptomatic (P30 to end stage), and adult symptomatic (P70 to end stage). Long-term adult fluoxetine treatment (started at either P30 or P70 and continuing until end stage) had no significant effect on disease progression. In contrast, neonatal fluoxetine treatment (P5-11) had two effects. First, all animals (mutant SOD1(G93A) and control: nontransgenic and SOD1(WT)) receiving the highest dose (10 mg/kg) had a sustained decrease in weight from P30 onward. Second, the high-dose SOD1(G93A) mice reached end stage ∼8 days (∼6% decrease in life span) sooner than vehicle and low-dose animals because of an increased rate of motor impairment. Fluoxetine increases synaptic serotonin (5-HT) levels, which is known to increase spinal motoneuron excitability. We confirmed that 5-HT increases spinal motoneuron excitability during this neonatal time period and therefore hypothesized that antagonizing 5-HT receptors during the same time period would improve disease outcome. However, cyproheptadine (1 or 5 mg/kg), a 5-HT receptor antagonist, had no effect on disease progression. These results show that a brief period of antidepressant treatment during a critical time window (the transition from neonatal to juvenile states) can be detrimental in ALS mouse models.

Effect of dichloromethane fraction of Areca catechu nut on monoamines associated behaviors and tyramine pressor sensitivity in rodents.

The current study was aimed at investigating the effect of Areca catechu nut dichloromethane fraction (7 mg/kg) on monoamines (serotonin and dopamine) modulation (5-hydroxytryptophan-induced tremors and phenylethylamine-induced stereotypes) and its interaction with tyramine (cheese effect). The dichloromethane fraction caused pronounced increase in 5-HTP-induced tremors (50%) with negligible PEA-induced stereotypes (20%). Additionally, it did not produce a significant increase in the tyramine pressor effects. These results suggest that the dichloromethane fraction of A. catechu nut primarily elevates serotonin levels (probably via monoamine oxidase A inhibition) and does not induce cheese effect.

Robust controller for tremor suppression at musculoskeletal level in human wrist.

Tremor is a rhythmical and involuntary oscillatory movement of a body part and it is one of the most common movement disorders. Orthotic devices have been under investigation as a noninvasive tremor suppression alternative to medication or surgery. The challenge in musculoskeletal tremor suppression is estimating and attenuating the tremor motion without impeding the patient's intentional motion. In this research a robust tremor suppression algorithm was derived for patients with pathological tremor in the upper limbs. First the motion in the tremor frequency range is estimated using a high-pass filter. Then, by applying the backstepping method the appropriate amount of torque is calculated to drive the output of the estimator toward zero. This is equivalent to an estimation of the tremor torque. It is shown that the arm/orthotic device control system is stable and the algorithm is robust despite inherent uncertainties in the open-loop human arm joint model. A human arm joint simulator, capable of emulating tremorous motion of a human arm joint was used to evaluate the proposed suppression algorithm experimentally for two types of tremor, Parkinson and essential. Experimental results show 30-42 dB (97.5-99.2%) suppression of tremor with minimal effect on the intentional motion.

Non-dopaminergic treatments for motor control in Parkinson's disease.

The pathological processes underlying Parkinson's disease (PD) involve more than dopamine cell loss within the midbrain. These non-dopaminergic neurotransmitters include noradrenergic, serotonergic, glutamatergic, and cholinergic systems within cortical, brainstem and basal ganglia regions. Several non-dopaminergic treatments are now in clinical use to treat motor symptoms of PD, or are being evaluated as potential therapies. Agents for symptomatic monotherapy and as adjunct to dopaminergic therapies for motor symptoms include adenosine A2A antagonists and the mixed monoamine-B inhibitor (MAO-BI) and glutamate release agent safinamide. The largest area of potential use for non-dopaminergic drugs is as add-on therapy for motor fluctuations. Thus adenosine A2A antagonists, safinamide, and the antiepileptic agent zonisamide can extend the duration of action of levodopa. To reduce levodopa-induced dyskinesia, drugs that target overactive glutamatergic neurotransmission can be used, and include the non-selective N-methyl D-aspartate antagonist amantadine. More recently, selective metabotropic glutamate receptor (mGluR5) antagonists are being evaluated in phase II randomized controlled trials. Serotonergic agents acting as 5-HT2A/2C antagonists, such as the atypical antipsychotic clozapine, may also reduce dyskinesia. 5-HT1A agonists theoretically can reduce dyskinesia, but in practice, may also worsen PD motor symptoms, and so clinical applicability has not yet been shown. Noradrenergic α2A antagonism using fipamezole can potentially reduce dyskinesia. Several non-dopaminergic agents have also been investigated to reduce non-levodopa-responsive motor symptoms such as gait and tremor. Thus the cholinesterase inhibitor donepezil showed mild benefit in gait, while the predominantly noradrenergic re-uptake inhibitor methylphenidate had conflicting results in advanced PD subjects. Tremor in PD may respond to muscarinic M4 cholinergic antagonists (anticholinergics), but tolerability is often poor. Alternatives include ß-adrenergic antagonists such as propranolol. Other options include 5-HT2A antagonists, and drugs that have mixed binding properties involving serotonin and acetylcholine, such as clozapine and the antidepressant mirtazapine, can be effective in reducing PD tremor. Many other non-dopaminergic agents are in preclinical and phase I/II early stages of study, and the reader is directed to recent reviews. While levodopa remains the most effective agent to treat motor symptoms in PD, the overall approach to using non-dopaminergic drugs in PD is to reduce reliance on levodopa and to target non-levodopa-responsive symptoms.

Pathological tremor prediction using surface electromyogram and acceleration: potential use in 'ON-OFF' demand driven deep brain stimulator design.

OBJECTIVE: We present a proof of concept for a novel method of predicting the onset of pathological tremor using non-invasively measured surface electromyogram (sEMG) and acceleration from tremor-affected extremities of patients with Parkinson's disease (PD) and essential tremor (ET). APPROACH: The tremor prediction algorithm uses a set of spectral (Fourier and wavelet) and nonlinear time series (entropy and recurrence rate) parameters extracted from the non-invasively recorded sEMG and acceleration signals. MAIN RESULTS: The resulting algorithm is shown to successfully predict tremor onset for all 91 trials recorded in 4 PD patients and for all 91 trials recorded in 4 ET patients. The predictor achieves a 100% sensitivity for all trials considered, along with an overall accuracy of 85.7% for all ET trials and 80.2% for all PD trials. By using a Pearson's chi-square test, the prediction results are shown to significantly differ from a random prediction outcome. SIGNIFICANCE: The tremor prediction algorithm can be potentially used for designing the next generation of non-invasive closed-loop predictive ON-OFF controllers for deep brain stimulation (DBS), used for suppressing pathological tremor in such patients. Such a system is based on alternating ON and OFF DBS periods, an incoming tremor being predicted during the time intervals when DBS is OFF, so as to turn DBS back ON. The prediction should be a few seconds before tremor re-appears so that the patient is tremor-free for the entire DBS ON-OFF cycle and the tremor-free DBS OFF interval should be maximized in order to minimize the current injected in the brain and battery usage.

The effects of antihistamines with varying anticholinergic properties on voluntary and involuntary movement.

OBJECTIVE: Recent evidence indicates that antihistamines can affect movement, which is most likely due to altered neurotransmission in cholinergic and histaminergic pathways. The purpose of this study was to determine if antihistamines with varying anticholinergic properties differentially affect voluntary and involuntary movement control. METHODS: Eleven healthy subjects were enlisted into a human double blind, placebo-controlled, five-way crossover study. Drowsiness, reaction time, and physiological tremor were examined 1-, 2-, and 3-hr post-ingestion of antihistamines with known anticholinergic profiles. These were the first-generation promethazine, and second-generation loratadine, desloratadine, and fexofenadine. Hyoscine butylbromide was used in an additional experiment to determine how a peripheral antimuscarinic drug influenced neuromotor function. RESULTS: Promethazine, desloratadine and fexofenadine increased drowsiness. Promethazine increased simple and choice reaction time and reduced tremor. Desloratadine increased choice reaction time and tremor, while loratadine slowed simple and choice reaction time. CONCLUSION: Central anticholinergic and antihistaminergic properties of antihistamines potentially contribute to movement dysfunction. SIGNIFICANCE: Second-generation antihistamines have provided the consumer with a safer alternative to the first-generation sedating antihistamine. However, the results of this study suggest that loratadine and desloratadine have the potential to affect movement control, and further research is warranted to understand the clinical relevance of these findings.

Tremorgenic mycotoxicosis in dogs.

Ingestion of tremorgenic mycotoxins formed in spoiled food can cause an acute tremor syndrome, the severity of which can range from mild to life-threatening. Swift recognition of the likely cause is required for accurate prognostication and rapid institution of appropriate therapy, which leads to complete resolution in most cases.