Compromised Motor Function Research Articles

Effectiveness and safety of intrathecal morphine for percutaneous endoscopic lumbar discectomy under low-dose ropivacaine: a prospective, randomized, double-blind clinical trial

BACKGROUND CONTEXTPercutaneous endoscopic lumbar discectomy (PELD) is a surgical setting that requires minimal motor impairment. Low-dose spinal ropivacaine induces little motor blockade and could be ideal for maintaining safety of PELD, but its analgesic efficacy is questionable. An adjunct analgesic approach is needed to maximize the benefits of low-dose spinal ropivacaine for PELD. PURPOSEThis study aimed to explore the effectiveness and safety of 100 µg intrathecal morphine (ITM) as an adjuvant analgesic method for PELD under low-dose spinal ropivacaine. STUDY DESIGNA double-blind, randomized, placebo-controlled trial. Trial registration: ChiCTR2000039842 (www.chictr.org.cn). SAMPLENinety patients scheduled for elective single-level PELD under low-dose spinal ropivacaine. OUTCOME MEASURESThe primary outcome was the overall intraoperative visual analogue scale (VAS) score for pain. Secondary outcomes were intraoperative VAS scores assessed at multiple timepoints; intraoperative rescue analgesic requirement; postoperative VAS scores; disability scale; patients’ satisfaction with anesthesia; adverse events; and radiographic outcomes. METHODSPatients were randomized to receive low-dose ropivacaine spinal anesthesia with (ITM group, n=45) or without (control group, n=45) 100 µg ITM. RESULTSThe overall intraoperative VAS score in the ITM group was significantly lower than that in the control group (0 [0, 1] vs 2 [1, 3], p<.001). During operation, the VAS scores at cannula insertion, 30 minutes after insertion, 60 minutes after insertion, and 120 minutes after insertion were all significantly lower in the ITM group (all p<.05). Less patients in the ITM group required rescue analgesia during operation compared with those in the control group (14% vs 42%, p= .003). The VAS score for back pain in the ITM group was lower than that in the control group at 1 hour, 12 hours, and 24 hours postoperatively. Besides, the satisfaction score in the ITM group was significantly higher than that in the control group (p=.017). For adverse events, 8/43 of ITM and 1/44 of control participants experienced pruritus (p=.014), with a relative risk (95% confidence interval) of 8.37 (1.09–64.16). The incidence of other adverse events was similar between the two groups. Of note, respiratory depression occurred in one ITM-treated patient. CONCLUSIONThe addition of 100 µg ITM to low-dose ropivacaine appears to be effective in analgesia without compromised motor function for PELD; however, ITM increased the risk of pruritus and clinicians should be vigilant about its potential risk of respiratory depression.

End-to-Side Nerve Transfer for the Management of Chronic Leg Compartment Ankle Dorsiflexion Weakness

Abstract Background A proximal deep peroneal nerve (DPN) injury can significantly impact the functional capacity of the leg, to include compromised motor function of the tibialis anterior (TA) muscle. Clinical examination can range from weakness in ankle dorsiflexion, to complete foot drop. Diagnostic nerve conduction velocity (NCV) testing can demonstrate abnormalities at select areas of impingement (or) entrapment (i.e., regions affected by a demyelinating compression mono-neuropathy), along the proximal course of the common peroneal nerve. Methods We retrospectively report on 17 patients with clinical weakness involving ankle dorsiflexion. All patients underwent surgical end-to-side anastomosis, transferring a muscular nerve branch from the superficial peroneal nerve (SPN) to a segment of the DPN responsible for TA muscle innervation. Outcomes were based on comparisons of preoperative and postoperative DPN motor function to the TA muscle, standardized to the British Medical Research Council Scale for Muscle Strength. Preoperative scores were generally M2 or below. Results Postoperative outcome scores of M4 to M5 were considered good (or) successful. 94.1% of patients demonstrated successful outcomes. Conclusion An end-to-side SPN motor branch anastomosis, into the motor branch of the DPN responsible for TA muscle innervation, can be a viable treatment option for weakness in ankle dorsiflexion. All reported cases involved a compromised segment of deep peroneal nerve within the proximal one-third of the leg.

Prevalence and Characteristics of Polyneuropathy in Atypical Parkinsonian Syndromes: An Explorative Study

(1) Background: Peripheral nerve involvement is increasingly recognized in Parkinson’s disease (PD). Although non-motor symptoms and postural instability are early features of atypical parkinsonian syndromes (APS), peripheral neuropathies in APS have not been addressed in detail thus far. Therefore, the aim of this study was to investigate the prevalence and characteristics of polyneuropathies (PNP) in multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), as representative syndromes of APS. (2) Methods: In total, 8 MSA and 6 PSP patients were comprehensively analyzed regarding subjective, clinical (motor and non-motor) and paraclinical PNP features using nerve conduction studies and high resolution nerve ultrasounds (HRUS). (3) Results: A total of 87.5% of MSA and 66.7% of PSP patients complained of at least one neuropathic symptom, with electrophysiological confirmation of PNP in 50.0% of both, MSA and PSP patients. PNP symptom severity in PSP and motor nerve amplitude in MSA were associated with compromised motor function. Morphologic nerve examination by HRUS showed few alterations according to the axonal type of PNP. (4) Conclusions: The overall high PNP symptom burden may be partially credited to the significant prevalence of electrophysiologically diagnosed PNP, and impact motor aspects of APS. The findings of this exploratory study reinforce further investigations on a larger scale, in order to elucidate peripheral nerve involvement and the underlying pathophysiological mechanisms of APS.

Generation of Neurodegenerative phenotype using Drosophila melanogaster through paraquat treatment and an amelioration by Tinospora cordifolia (giloy)

Neurodegenerative diseases are non-curable for the modern world and mainly affecting the aged population across the globe. These diseases cause serious issues with compromised motor function and along with dementia. In the present study, we have explored the benefits of Tinospora cordifolia (giloy) against chemical-induced neurodegeneration in wild type Drosophila melanogaster (Oregon R+) also known as fruit fly. We examined the biochemical properties of Tinospora cordifolia (giloy) through phenolic content and antioxidant capacity. The antioxidant activities of giloy were judged by in vitro methods like total phenolic content and DPPH free radical scavenging assay against ascorbic acid as standard. We treated D. melanogaster with paraquat (PQ, 1.0mM and 2.0mM) for 24 and 48 h and after the treatment, neurodegeneration was evaluated through classical methods like locomotor assay and memory assay in fruit flies. Furthermore, we have also checked the impact of paraquat on the total survival of the flies to evaluat lonevity and we evident a significant amelioration in neurodegeneration due to co-treatment of Tinospora cordifolia as compared to paraquat-treated flies. We found an improved toal survival of D. melanogaster in PQ along with Tinospora cordifolia treated groups and evident a significant difference in locomotor as well as in memory assays. Conclusively, we may suggest that Tinospora cordifolia is having good phenolic content and free radical scavenging properties thereby D. melanogaster treated along with giloy exhibited reduced neurodegeneration and showed significant amelioration.

Depression-like behavior corresponds with cardiac changes in a rodent model of spinal cord injury

In previous studies we have shown that approximately 1/3 of male Sprague Dawley rats develop symptoms of depression following a spinal cord injury (SCI). Using established behavioral tests to measure depression in rodents, we found that after SCI, subjects characterized as depressed had decreased sucrose preference, open field activity, social exploration, and burrowing behavior. As some of these tests of depression could be affected by the compromised motor function inherent to the SCI condition, the current study examined whether non-subjective, physiological differences in heart rate and heart rate variability were also associated with depression, as seen in humans. Male Sprague Dawley rats were implanted with radiotelemetry devices and either received a moderate contusion injury or remained intact. The implanted telemetry devices recorded home cage activity, body temperature, heart rate, and heart rate variability for 5 min/h throughout a 30-day post-injury assessment period. Depression behavior was evaluated using a battery of tests conducted on days 9–10 and 19–20 post-injury. Locomotor recovery and pain reactivity were also examined. Hierarchical clustering, based on the behavioral scores collected on the tests of depression, revealed that 28% of the SCI subjects displayed symptoms of depression, relative to the remaining 72% of SCI subjects. The subjects characterized as depressed had significantly lower social interaction and burrowing activity than the group that was not depressed. Interestingly, the subjects behaviorally characterized as depressed also had significantly lower heart rate variability than the not-depressed intact group. There was no difference between not-depressed SCI and intact rats on this measure. Therefore, in addition to behavior, depressed and not-depressed rats differ on measures of physiological function that are associated with depression in humans. These physiological differences further validate the rodent model of depression after SCI.

Decoding brain-computer interfaces

Neuroengineering Brain-computer interfaces (BCIs) can help humans with compromised motor function by using their brain activity to externally control movements. Existing methods, however, require extensive user training and effort. Ganesh et al. developed a BCI technique for decoding sensorimotor prediction errors that requires less user energy. It subliminally stimulates the user to think about an activity and then, instead of decoding what movement a user intends, decodes whether the movement that the user wants matches the sensory feedback that the stimulator induced. In 12 healthy individuals performing a wheelchair-turning task, this interface represented movements speedily (within 96 milliseconds) and without any training. Sci. Adv. 10.1126/sciadv.aaq0183 (2018).

Hybrid Blocks for Total Knee Arthroplasty: A Technical Description.

This narrative review article aims to examine current evidence of knee innervation in order to develop a technique of targeting pure sensory innervation of the knee joint without compromising motor function. A literature review of knee innervation was performed to gain an anatomic understanding of terminal sensory branches of the relevant target nerves (femoral, obturator, sciatic, and lateral femoral cutaneous). Pure sensory block of the knee joint is challenging due to important contributions from themuscular innervation close to the joint and the variability of nerves afferents contained within and around the adductor canal. On the basis of this anatomic knowledge we describe an ultrasound-guided 3-injection hybrid technique that represents a balance between preserving adequate motor power while still providing analgesia in a simple method.

Constitutive activity of 5-HT2C receptors is present after incomplete spinal cord injury but is not modified after chronic SSRI or baclofen treatment.

After spinal cord injury (SCI), reflexes become hyperexcitable, leading to debilitating muscle spasms and compromised motor function. Previous work has described adaptations in spinal systems that might underlie this hyperexcitability, including an increase in constitutively active 5-HT2C receptors in spinal motoneurons. That work, however, examined adaptations following complete transection SCI, whereas SCI in humans is usually anatomically and functionally incomplete. We therefore evaluated whether constitutive activity of 5-HT2C receptors contributes to reflex hyperexcitability in an incomplete compression model of SCI and to spasms in vitro and in vivo. Our results confirm that 5-HT2C receptor constitutive activity contributes to reflex excitability after incomplete SCI. We also evaluated whether constitutive activity could be altered by manipulation of neural activity levels after SCI, testing the hypothesis that it reflects homeostatic processes acting to maintain spinal excitability. We decreased neural activity after SCI by administering baclofen and increased activity by administering the selective serotonin reuptake inhibitor (SSRI) fluoxetine. We found that drug administration produced minimal alterations in in vivo locomotor function or reflex excitability. Similarly, we found that neither baclofen nor fluoxetine altered the contribution of constitutively active 5-HT2C receptors to reflexes after SCI, although the contribution of 5-HT2C receptors to reflex activity was altered after SSRIs. These results confirm the importance of constitutive activity in 5-HT2C receptors to spinal hyperexcitability following SCI in the clinically relevant case of incomplete SCI but suggest that this activity is not driven by homeostatic processes that act to maintain overall levels of spinal excitability.NEW & NOTEWORTHY After spinal cord injury (SCI), most people will develop muscle spasms below their level of injury that can severely impact function. In this work, we examine the adaptations that occur within the spinal cord after SCI that contribute to these motor dysfunctions. We also evaluate one hypothesis about how these adaptations develop, which will potentially lead to intervention strategies to improve functional outcomes in persons with SCI.

Discovery of Compounds that Positively Modulate the High Affinity Choline Transporter.

Cholinergic hypofunction is associated with decreased attention and cognitive deficits in the central nervous system in addition to compromised motor function. Consequently, stimulation of cholinergic neurotransmission is a rational therapeutic approach for the potential treatment of a variety of neurological conditions. High affinity choline uptake (HACU) into acetylcholine (ACh)-synthesizing neurons is critically mediated by the sodium- and pH-dependent high-affinity choline transporter (CHT, encoded by the SLC5A7 gene). This transporter is comparatively well-characterized but otherwise unexplored as a potential drug target. We therefore sought to identify small molecules that would enable testing of the hypothesis that positive modulation of CHT mediated transport would enhance activity-dependent cholinergic signaling. We utilized existing and novel screening techniques for their ability to reveal both positive and negative modulation of CHT using literature tools. A screening campaign was initiated with a bespoke compound library comprising both the Pfizer Chemogenomic Library (CGL) of 2,753 molecules designed specifically to help enable the elucidation of new mechanisms in phenotypic screens and 887 compounds from a virtual screening campaign to select molecules with field-based similarities to reported negative and positive allosteric modulators. We identified a number of previously unknown active and structurally distinct molecules that could be used as tools to further explore CHT biology or as a starting point for further medicinal chemistry.

Stimulating at the right time: phase-specific deep brain stimulation.

SEE MOLL AND ENGEL DOI101093/AWW308 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Brain regions dynamically engage and disengage with one another to execute everyday actions from movement to decision making. Pathologies such as Parkinson's disease and tremor emerge when brain regions controlling movement cannot readily decouple, compromising motor function. Here, we propose a novel stimulation strategy that selectively regulates neural synchrony through phase-specific stimulation. We demonstrate for the first time the therapeutic potential of such a stimulation strategy for the treatment of patients with pathological tremor. Symptom suppression is achieved by delivering stimulation to the ventrolateral thalamus, timed according to the patient's tremor rhythm. Sustained locking of deep brain stimulation to a particular phase of tremor afforded clinically significant tremor relief (up to 87% tremor suppression) in selected patients with essential tremor despite delivering less than half the energy of conventional high frequency stimulation. Phase-specific stimulation efficacy depended on the resonant characteristics of the underlying tremor network. Selective regulation of neural synchrony through phase-locked stimulation has the potential to both increase the efficiency of therapy and to minimize stimulation-induced side effects.

Functional and Morphological Correlates in the Drosophila LRRK2 loss-of-function Model of Parkinson's Disease: Drug Effects of Withania somnifera (Dunal) Administration.

The common fruit fly Drosophila melanogaster (Dm) is a simple animal species that contributed significantly to the development of neurobiology whose leucine-rich repeat kinase 2 mutants (LRRK2) loss-of-function in the WD40 domain represent a very interesting tool to look into physiopathology of Parkinson’s disease (PD). Accordingly, LRRK2 Dm have also the potential to contribute to reveal innovative therapeutic approaches to its treatment. Withania somnifera Dunal, a plant that grows spontaneously also in Mediterranean regions, is known in folk medicine for its anti-inflammatory and protective properties against neurodegeneration. The aim of this study was to evaluate the neuroprotective effects of its standardized root methanolic extract (Wse) on the LRRK2 loss-of-function Dm model of PD. To this end mutant and wild type (WT) flies were administered Wse, through diet, at different concentrations as larvae and adults (L+/A+) or as adults (L-/A+) only. LRRK2 mutants have a significantly reduced lifespan and compromised motor function and mitochondrial morphology compared to WT flies 1% Wse-enriched diet, administered to Dm LRRK2 as L-/A+and improved a) locomotor activity b) muscle electrophysiological response to stimuli and also c) protected against mitochondria degeneration. In contrast, the administration of Wse to Dm LRRK2 as L+/A+, no matter at which concentration, worsened lifespan and determined the appearance of increased endosomal activity in the thoracic ganglia. These results, while confirming that the LRRK2 loss-of-function in the WD40 domain represents a valid model of PD, reveal that under appropriate concentrations Wse can be usefully employed to counteract some deficits associated with the disease. However, a careful assessment of the risks, likely related to the impaired endosomal activity, is required.

The GLP-1 receptor agonist liraglutide reduces pathology-specific tau phosphorylation and improves motor function in a transgenic hTauP301L mouse model of tauopathy

In addition to a prominent role in glycemic control, glucagon-like peptide 1 (GLP-1) receptor agonists exhibit neuroprotective properties. There is mounting experimental evidence that GLP-1 receptor agonists, including liraglutide, may enhance synaptic plasticity, counteract cognitive deficits and ameliorate neurodegenerative features in preclinical models of Alzheimer’s disease (AD), predominantly in the context of β-amyloid toxicity. Here we characterized the effects of liraglutide in a transgenic mutant tau (hTauP301L) mouse tauopathy model, which develops age-dependent pathology-specific neuronal tau phosphorylation and neurofibrillary tangle formation with progressively compromised motor function (limb clasping). Liraglutide (500µg/kg/day, s.c., q.d., n=18) or vehicle (n=18) was administered to hTauP301L mice for 6 months from the age of three months. Vehicle-dosed wild-type FVB/N mice served as normal control (n=17). The onset and severity of hind limb clasping was markedly different in liraglutide and vehicle-dosed transgenic mice. Clasping behavior was observed in 61% of vehicle-dosed hTauP301L mice with a 55% survival rate in 9-month old transgenic mice. In contrast, liraglutide treatment reduced the clasping rate to 39% of hTauP301L mice, and fully prevented clasping-associated lethality resulting in a survival rate of 89%. Stereological analyses demonstrated that hTauP301L mice exhibited hindbrain-dominant neuronal accumulation of phosphorylated tau closely correlated to the severity of clasping behavior. In correspondence, liraglutide treatment significantly reduced neuronal phospho-tau load by 61.9±10.2% (p<0.001) in hTauP301L mice, as compared to vehicle-dosed controls. In conclusion, liraglutide significantly reduced tau pathology in a transgenic mouse tauopathy model.

Assessing neuro-motor recovery in a stroke survivor with high-resolution EEG, robotics and Virtual Reality.

One post-stroke patient underwent neuro-motor rehabilitation of one upper limb with a novel system combining a passive robotic device, Virtual Reality training applications and high resolution electroencephalography (HR-EEG). The outcome of the clinical tests and the evaluation of the kinematic parameters recorded with the robotic device concurred to highlight an improved motor recovery of the impaired limb despite the age of the patient, his compromised motor function, and the start of rehabilitation at the 3rd week post stroke. The time frequency and functional source analysis of the HR-EEG signals permitted to quantify the functional changes occurring in the brain in association with the rehabilitation motor tasks, and to highlight the recovery of the neuro-motor function.

Physiological Function of Gastrin-Releasing Peptide and Neuromedin B Receptors in Regulating Itch Scratching Behavior in the Spinal Cord of Mice

Pruritus (itch) is a severe side effect associated with the use of drugs as well as hepatic and hematological disorders. Previous studies in rodents suggest that bombesin receptor subtypes i.e. receptors for gastrin-releasing peptide (GRPr) and neuromedin B (NMBr) differentially regulate itch scratching. However, to what degree spinal GRPr and NMBr regulate scratching evoked by intrathecally administered bombesin-related peptides is not known. The first aim of this study was to pharmacologically compare the dose-response curves for scratching induced by intrathecally administered bombesin-related peptides versus morphine, which is known to elicit itch in humans. The second aim was to determine if spinal GRPr and NMBr selectively or generally mediate scratching behavior. Mice received intrathecal injection of bombesin (0.01–0.3 nmol), GRP (0.01–0.3nmol), NMB (0.1–1nmol) or morphine (0.3–3 nmol) and were observed for one hour for scratching activity. Bombesin elicited most profound scratching over one hour followed by GRP and NMB, whereas morphine failed to evoke scratching response indicating the insensitivity of mouse models to intrathecal opioid-induced itch. Intrathecal pretreatment with GRPr antagonist RC-3095 (0.03–0.1 nmol) produced a parallel rightward shift in the dose response curve of GRP-induced scratching but not NMB-induced scratching. Similarly, PD168368 (1–3 nmol) only attenuated NMB but not GRP-induced scratching. Individual or co-administration of RC-3095 and PD168368 failed to alter bombesin-evoked scratching. A higher dose of RC-3095 (0.3 nmol) generally suppressed scratching induced by all three peptides but also compromised motor function in the rotarod test. Together, these data indicate that spinal GRPr and NMBr independently drive itch neurotransmission in mice and may not mediate bombesin-induced scratching. GRPr antagonists at functionally receptor-selective doses only block spinal GRP-elicited scratching but the suppression of scratching at higher doses is confounded by motor impairment.

Physical activity and obesity mediate the association between childhood motor function and adolescents’ academic achievement

The global epidemic of obesity and physical inactivity may have detrimental implications for young people's cognitive function and academic achievement. This prospective study investigated whether childhood motor function predicts later academic achievement via physical activity, fitness, and obesity. The study sample included 8,061 children from the Northern Finland Birth Cohort 1986, which contains data about parent-reported motor function at age 8 y and self-reported physical activity, predicted cardiorespiratory fitness (cycle ergometer test), obesity (body weight and height), and academic achievement (grades) at age 16 y. Structural equation models with unstandardized (B) and standardized (β) coefficients were used to test whether, and to what extent, physical activity, cardiorespiratory fitness, and obesity at age 16 mediated the association between childhood motor function and adolescents' academic achievement. Physical activity was associated with a higher grade-point average, and obesity was associated with a lower grade-point average in adolescence. Furthermore, compromised motor function in childhood had a negative indirect effect on adolescents' academic achievement via physical inactivity (B = -0.023, 95% confidence interval = -0.031, -0.015) and obesity (B = -0.025, 95% confidence interval = -0.039, -0.011), but not via cardiorespiratory fitness. These results suggest that physical activity and obesity may mediate the association between childhood motor function and adolescents' academic achievement. Compromised motor function in childhood may represent an important factor driving the effects of obesity and physical inactivity on academic underachievement.

Regional Nerve Block of the Upper Eyelid in Oculoplastic Surgery

To establish the efficacy of a regional nerve block of the upper eyelid and its effect on levator motor function. Forty-one patients underwent surgery on 54 upper eyelids by one surgeon, after administration of a regional nerve block at the supraorbital notch. The amount of pain experienced by patients due to the local anesthetic injection and surgery was determined by using visual analogue scores. The effect of the local anesthetic injection on levator function was determined by comparing the measured levator function prior to and following administration. Any complications attributable to the regional sensory nerve block were recorded. Ninety-two percent of patients found the injection painless, and the rest reported negligible pain. The mean pain score for the injection was 2 (SD 1.3, range 0-6). The mean pain score for the surgery was 0.3 (SD 0.6, range 0-3). No significant difference was found in levator function prior to and following the injection (pre-function: 14.4 mm, post-function: 13.4 mm, p=0.01). One patient had hematoma formation at the site of injection. A regional nerve block of the upper eyelid achieves effective sensory anesthesia,without compromising motor function. This helps in an accurate assessment of intraoperative height during upper lid surgery.

Impaired Glutamate Transport in a Mouse Model of Tau Pathology in Astrocytes

Filamentous tau inclusions in neurons and glia are neuropathological hallmarks of tauopathies. The discovery of microtubule-associated protein tau gene mutations that are pathogenic for a heterogenous group of neurodegenerative disorders, called frontotemporal dementia and parkinsonism linked to chromosome-17 (FTDP-17), directly implicate tau abnormalities in the onset/progression of disease. Although the role of tau pathology in neurons in disease pathogenesis is well accepted, the contribution of glial pathology is essentially unknown. We recently generated a transgenic (Tg) mouse model of tau pathology in astrocytes by expressing the human tau protein under the control of the glial fibrillary acidic protein (GFAP) promoter. Both wild-type and FTDP-17 mutant GFAP/tau Tg animals manifest an age-dependent accumulation of tau inclusions in astrocytes that resembles the pathology observed in human tauopathies. We further demonstrate that both strains of Tg mice manifest compromised motor function that correlates with altered expression of the glial glutamate-aspartate transporter and occurs before the development of tau pathology. Subsequently, the Tg mice manifest additional deficits in neuromuscular strength that correlates with reduced expression of glutamate transporter-1 (GLT-1) and occurs concurrent with tau inclusion pathology. Reduced GLT-1 expression was associated with a progressive decrease in sodium-dependent glutamate transport capacity. Reductions in GLT-1 expression were also observed in corticobasal degeneration, a tauopathy with prominent pathology in astrocytes. Less robust changes were observed in Alzheimer's disease in which neuronal tau pathology predominates. Thus, these Tg mice recapitulate features of astrocytic pathology observed in tauopathies and implicate a role for altered astrocyte function in the pathogenesis of these disorders.

Analgesia and anaesthesia in labour

Analgesia is often required in labour for both humanitarian and medical reasons. Although many techniques are used to provide analgesia in labour, neuraxial (epidural or intrathecal) analgesia is the only technique capable of producing complete pain relief. The use of analgesia in labour is influenced by parity, duration of labour, experience in a previous labour and the induction as opposed to the spontaneous onset of labour. Modern epidural techniques aim to achieve pain relief without compromising motor function and the ability to push in the second stage. This is achieved by using low concentrations of local anaesthetic (bupivacaine 0.065–0.10%) and opioid solutions. Maternal mortality associated with anaesthesia has fallen dramatically in the past 50 years consequent to the increased use of regional anaesthesia for obstetric surgery, together with the more focused training of anaesthetists.

MANAGEMENT OF PSYCHOSIS IN PARKINSON'S DISEASE

SUMMARYPsychosis is one of the most disabling complications associated with Parkinson's disease (PD) and occurs in up to 30% of PD patients treated chronically with antiparkinsonian drugs. Visual hallucinations, with or without delirium and paranoid delusions, are the most frequent symptoms. Psychosis complicating PD can be more disabling than the motor symptoms of PD; it frequently poses a serious threat to the patient's ability to maintain independence and is the single greatest risk factor for nursing home placement. Choosing an antipsychotic drug for a PD patient is a common clinical dilemma. The conventional antipsychotic drugs are poorly tolerated in PD because of their predictable and at times profound worsening in parkinsonian motor symptoms. The recent availability of atypical antipsychotic drugs that can control psychotic symptoms without compromising motor function has led to significant advances in therapeutic strategies in the management of PD psychosis in the community. This article reviews data on the use of atypical antipsychotics in patients with PD and the current recommendations on their use in the management of PD psychosis.

Treatment of psychosis in Parkinson's disease: safety considerations.

Psychosis only rarely occurs in patients with untreated Parkinson's disease. Much more commonly, psychosis is induced by drug therapy for Parkinson's disease and is the strongest known risk factor for nursing home placement. Delusions are less frequent than hallucinations, but are more concerning as they are often paranoid in nature. Treatment begins with a search for correctable infectious, toxic, and metabolic aetiologies. If symptoms persist, anti-Parkinson's disease medications are slowly reduced. However, withdrawal of these drugs usually worsens parkinsonism and is often not tolerated. Certain atypical antipsychotics can be used to treat psychosis without compromising motor function. The choice of atypical antipsychotic is largely based on ease of use and adverse effect profile as most have comparable efficacy in improving psychosis. Currently, there are five marketed atypical drugs - clozapine, risperidone, olanzapine, quetiapine and ziprasidone. Ziprasidone is the only agent whose adverse effect profile has not been reported in Parkinson's disease. The most common adverse effects of clozapine in Parkinson's disease are sedation, orthostatic hypotension and sialorrhoea. Sedation is generally helpful since these patients are frequently awake at night and tend to have worse behavioural problems then. Clozapine does not induce deterioration of motor function, but it has the potential to cause agranulocytosis, which is idiosyncratic and not dose-related. In risperidone-treated Parkinson's disease patients, reported adverse effects include somnolence, sialorrhoea, dizziness, palpitations, constipation, delirium, fatigue, leg cramps, depression, urinary incontinence and hypotension. Although in some Parkinson's disease studies, risperidone has been well tolerated, others have shown that many patients are unable to tolerate the drug due to deterioration of motor function. While an initial study of olanzapine in Parkinson's disease psychosis showed the drug to be effective without deterioration of motor function, succeeding reports demonstrated a deleterious effect of the drug on motor functioning. The most common adverse effects of quetiapine in Parkinson's disease patients are sedation and orthostatic hypotension. There is a lack of double-blind trials; however, cumulative reports involving >200 Parkinson's disease patients strongly suggest that quetiapine is well tolerated and effective. Unlike clozapine, it does not improve tremor and may induce mild deterioration of motor function. Recently, cholinesterase inhibitors have been reported to alleviate psychosis in Parkinson's disease. Although ondansetron, an antiemetic with antiserotonergic properties, has been reported to relieve psychosis in Parkinson's disease, its prohibitive cost has prevented further study in this population. Electroconvulsive treatment is generally reserved for the patient with psychotic depression who is unable to tolerate any pharmacological therapy.