ATP1A3 related disease manifesting as rapid onset dystonia-parkinsonism with prominent myoclonus and exaggerated startle.

We report ATP1A3-associated rapid-onset dystonia-parkinsonism with an atypical presentation including myoclonus and exaggerated startle in four patients. Their prominence over parkinsonism prompted consideration of a syndromic diagnosis of myoclonus dystonia. ATP1α3 dysfunction in GABAergic neurons could explain these examination findings. The spectrum of ATP1A3-associated movement disorders includes myoclonus-dystonia.

A cross-sectional study of walking, balance and upper limb assessment scales in people with cervical dystonia.

Cervical dystonia (CD) is a neurological movement disorder causing the neck to move involuntarily away from the neutral position. CD is a network disorder, involving multiple brain areas and, therefore, may impair movement in parts of the body other than the neck. This study used clinical assessments to investigate walking, balance and upper limb function (UL) in people with CD; the reliability of scoring these assessments and examined for relationship between CD severity, usual exercise and clinical assessments. We conducted a prospective observational cohort study of participants with isolated, focal, idiopathic CD. Participants were assessed by experienced physiotherapists and completed three questionnaires and eight clinical assessments of fear of falling, balance confidence, walking, balance, UL function and usual exercise. Results were compared to published data from healthy adults and other neurological populations. Twenty-two people with mild to moderate CD participated. Fear of falling, gross UL function and usual exercise were worse in people with CD compared with healthy adults, while walking, balance and distal UL function were similar to healthy populations. All assessments were reliably performed by physiotherapists, and we found no correlations between the severity of dystonia or usual exercise and performance on the physical assessments. Routine performance of clinical assessment of walking and balance are likely not required in people with mild to moderate CD; however, fear of falling and gross upper limb function should be assessed to determine any problems which may be amenable to therapy.

Validation of Fear of Falling and Balance Confidence Assessment Scales in Persons With Dystonia.

BACKGROUND AND PURPOSE: Falls are problematic for people living with neurological disorders and a fear of falling can impact on actual falls. Fear of falling is commonly assessed using the Falls Self-Efficacy Scale International (FES-I) or the Activities-specific Balance Confidence (ABC) Scale. These scales can predict risk of falling. We aimed to validate the FES-I and the ABC in persons with dystonia. METHODS: We conducted an online survey of people with dystonia, collecting information on demographics, 6-month falls history, dystonia disability, and the FES-I and ABC scales. Scales were validated for structural validity and internal consistency. We also examined goodness-of-fit, convergent validity, and predictive validity, and determined cutoff scores for predicting falls risk. RESULTS: Survey responses (n = 122) showed that both FES-I and ABC scales have high internal validity and convergent validity with the Functional Disability Questionnaire in persons with dystonia. Each scale examines a single factor, fear of falling (FES-I) and balance confidence (ABC). At least one fall was reported by 39% of participants; the cutoff value for falls risk was found to be 29.5 and 71.3 for the FES-I and the ABC respectively. DISCUSSION AND CONCLUSIONS: The FES-I and the ABC scales are valid scales to examine fear of falling and balance confidence in persons with dystonia. Fear of falling is high and balance confidence is low and both are worse in those with dystonia who have previously fallen.Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A182).

Functional gait disorder.

Gait disorder is a common accompaniment of functional neurologic disorders. The diagnosis of a functional or psychogenic gait is complex. It requires a sound knowledge of the range of phenomenology observed in organic movement disorders, the ability to evaluate and diagnose nonmovement disorder neurologic symptoms and signs, but additionally knowledge of potential musculoskeletal causes of gait disturbance. A stepwise approach to the analysis of the phenomenology and separation into four (sometimes overlapping) psychogenic gait syndromes is suggested to aid diagnosis: (1) movement disorder mimics; (2) neurologic (nonmovement disorder) mimics; (3) musculoskeletal or biomechanical mimics; and (4) isolated disequilibrium or balance disorders. Accurate diagnosis can lead to effective therapy.

Four cases of orthostatic myoclonus.

Orthostatic unsteadiness (unsteadiness on standing) is a relatively common symptom and can have neurological or non-neurological causes. Glass et al. have recently described a syndrome presenting with unsteadiness or leg jerking during standing or gait initiation difficulty which they have termed orthostatic myoclonus (OM). OM is a disabling syndrome but potentially treatable. It may develop on the background of neurodegenerative disease; other causes include pro-myoclonic drugs such as tricyclic antidepressants. In order to increase awareness of this syndrome, we report four patients with electrophysiologically confirmed OM who were referred to the movement disorder unit for lower limb tremor studies. All four patients presented with unsteadiness on standing. There were no signs suggestive of neurodegenerative disease and three of the patients had a provisional diagnosis of orthostatic tremor. The diagnosis of OM was supported by a surface electromyography showing 9-16Hz, non-rhythmic muscle bursts with burst duration of 50-100ms during standing. OM is unrecognised by many physicians as a cause of orthostatic intolerance. The most common syndrome with which OM may be confused is orthostatic tremor. A correct diagnosis is important as it may respond to treatment with clonazepam, gabapentin or piracetam.

Reduced muscle strength is the major determinant of reduced leg muscle power in Parkinson's disease.

BACKGROUND: Reduced muscle power (speed × strength) is associated with increased fall risk and reduced walking speed in people with Parkinson's disease (PD) as well as in the general older population. This study aimed to determine the relative contribution of motor impairments (bradykinesia, tremor, rigidity and weakness) to reduced leg muscle power in people with PD. METHODS: Eighty-two people with PD were tested while "on" medication. Leg extensor muscle strength and muscle power were measured using pneumatic variable resistance equipment. Lower limb bradykinesia, rigidity and tremor were measured using the Movement Disorders Society-sponsored Unified Parkinson's Disease Rating Scale. Associations between motor impairments and leg muscle power were examined using linear regression. RESULTS: Univariate models revealed that muscle strength (R(2) = 0.84), bradykinesia (R(2) = 0.05) and rigidity (R(2) = 0.05) were significantly associated with leg muscle power, while tremor was not. A multivariate model including bradykinesia, tremor, rigidity, muscle strength, age and gender explained 89% of the variance in leg muscle power. This model revealed reduced muscle strength to be the major determinant of reduced muscle power (ß = 0.7), while bradykinesia was a minor contributor to reduced muscle power (ß = -0.1), even when accounting for age and gender. CONCLUSIONS: The findings that reduced strength and bradykinesia contribute to reduced muscle power in people with PD tested "on" medication suggest that these impairments are potential targets for physical interventions.

Delayed-onset focal dystonia of the leg secondary to traumatic brain injury.

A 42-year-old man presented with action-induced, stereotyped posturing of the left leg with task specificity following major traumatic brain injury less than a year earlier. Although adult onset primary leg dystonia is a recognised entity, our patient is unusual in that dystonia was an isolated abnormality without associated spasticity, was not preceded by ipsilateral hemiparesis and remained focal without progression to involve other body regions. MRI brain showed a small area of gliosis in the left frontal subcortical white matter but with no lesions in the basal ganglia or thalamus. The dystonia in our patient almost completely resolved with botulinum toxin therapy.

Botulinum toxin assessment, intervention and aftercare for lower limb disorders of movement and muscle tone in adults: international consensus statement.

Lower limb disorders of movement and muscle tone in adults significantly impact quality of life. The management of the patient with hypertonia is complex and requires a multidisciplinary team working with the patient and family/carers. Botulinum neurotoxin type A (BoNT-A) has been used as a component of this management to reduce lower limb hypertonia, increase passive range of motion and reduce associated pain and requirements for bracing. Adjunctive treatments to augment the effect of BoNT-A include electrical muscle stimulation of the injected muscles and stretching. When determining suitability for injection, the patient's main goals for intervention need to be established. Muscle overactivity must be distinguished from contracture, and the effect of underlying muscle weakness taken into account. Explanation of the injection process, potential adverse effects and post-injection interventions is essential. Assessment at baseline and post-treatment of impairments such as hypertonia, range of motion and muscle spasm are appropriate; however, the Goal Attainment Scale and other validated patient-centred scales can also be useful to assess therapy outcomes. In the future, initiatives should be directed towards examining the effectiveness of BoNT treatment to assist with achievement of functional and participation goals in adults with hypertonia and dystonia affecting the lower limb.

Botulinum toxin assessment, intervention and aftercare for cervical dystonia and other causes of hypertonia of the neck: international consensus statement.

Dystonia in the neck region can be safely and effectively reduced with injections of Botulinum neurotoxin-A and B. People with idiopathic cervical dystonia have been studied the most. Benefits following injection include increased range of movement at the neck for head turning, decreased pain, and increased functional capacity (Class I evidence, level A recommendation). The evidence for efficacy and safety in patients with secondary dystonia in the neck is unclear based on the lack of rigorous research conducted in this heterogeneous population (level U recommendation). Psychometrically sound assessments and outcome measures exist to guide decision-making (Class I evidence, level A recommendation). Much less is known about the effectiveness of therapy to augment the effects of the injection (Class IV, level U recommendation). More research is needed to answer questions about safety and efficacy in secondary spastic neck dystonia, effective adjunctive therapy, dosing and favourable injection techniques.

Botulinum toxin assessment, intervention and aftercare for paediatric and adult niche indications including pain: international consensus statement.

Evidence is emerging for the use of botulinum neurotoxin type-A (BoNT-A) for niche indications including pain independent of spasticity. Pain indications such as chronic nociceptive back pain, piriformis syndrome, chronic myofascial pain, pelvic pain, complex regional pain syndrome, facial pain and neuropathic pain are outlined in this paper. Of these, class I evidence is available for the treatment of chronic nociceptive low back pain, piriformis syndrome, myofascial pain, facial pain, neuropathic pain and plantar fasciitis. Peri-operative use of BoNT-A is emerging, with indications including planning for surgery and facilitating surgery, as well as healing and improving analgesia post-operatively. Evidence is limited, although there are some reports that clinicians are successfully using BoNT-A peri-operatively. There is class I evidence showing pre-operative use of BoNT-A has a beneficial effect on outcomes following adductor-release surgery. The use of BoNT for treatment of tremor, other than neck tremor in the setting of cervical dystonia, including evidence for upper limb tremor, cranial tremor and non-dystonic neck tremor is reviewed. The evidence is variable at this stage, and further study is required to develop definitive recommendations for the clinical utility of BoNT-A for these indications.

Reduced muscle power is associated with slower walking velocity and falls in people with Parkinson's disease.

PURPOSE: Muscle strength (force) and power (force x velocity) are reduced in Parkinson's disease (PD). Reduced muscle power is associated with slower walking velocity and falls in the older population, but these associations in people with PD have not previously been investigated. This study investigated the relationships between leg extensor muscle power and strength with walking speed and past falls in people with PD. PARTICIPANTS AND METHODS: Forty people with mild to moderate PD were assessed. Walking velocity was measured over 10 m and the number of falls the participant reported having in the past 12 months was recorded. Leg extensor muscle power and strength were measured using a Keiser leg press machine. RESULTS: Muscle power explained more than half of the variance (R(2) = 0.54) in walking velocity and remained significantly (p < 0.05) associated with walking velocity in models which included Unified Parkinson's Disease Rating Scale (UPDRS) motor scores. Participants with low muscle power were 6 times more likely to report multiple falls in the past year than those with high muscle power (OR = 6.0, 95% CI 1.1 to 33.3), though this association between falls and power was no longer significant in models which included UPDRS motor scores (p = 0.09). CONCLUSION: Muscle power is a significant determinant of walking velocity in PD even after adjusting for UPDRS motor score. Muscle power training warrants investigation in people with PD.

Anti-melanin antibodies are increased in sera in Parkinson's disease.

An increasing body of research suggests that a number of immune mechanisms play a role in degenerative pathways in Parkinson's disease (PD). In the current work we investigated a posited humoral immune response in this disorder. Sera from PD patients exhibited a significantly enhanced absorbance response on a novel ELISA for anti-melanin antibodies, compared to sera from age-matched control subjects. The enhanced ELISA absorbance response was specific for catecholamine-based melanins and was unrelated to antiparkinsonian dopaminergic medication. Further, the absorbance response was significantly and negatively correlated with disease duration. These data suggest that a specific humoral anti-melanin antibody response is present in PD and is more active in early disease. While the contribution of this novel immune response to the initiation and progression of this disorder is unclear, this finding supports the hypothesis that specific immune responses occurring in PD may respond to therapeutic interventions in this disorder.

Acute and reversible micrographia in a patient possibly due to cerebral ischaemia.

We report a patient who developed acute and reversible micrographia, presumably due to cerebral ischaemia, on a background of mutism following a pharyngo-laryngectomy 10 years earlier. Magnetic resonance (MR) imaging showed chronic small vessel disease without evidence of an acute ischaemic lesion on diffusion-weighted sequences. Our patient's micrographia improved significantly within 12 days of symptom onset. The MR imaging was performed within 5 days of symptom onset, suggesting that the lesion was either too small for detection or had resolved on diffusion-weighted sequences.

The contribution of tremor studies to diagnosis of parkinsonian and essential tremor: a statistical evaluation.

This study statistically evaluated a set of commonly measured tremor parameters to determine their individual and combined ability to discriminate between essential tremor (ET) and Parkinsonian tremor (PT). Accelerometer and surface electromyographic (EMG) records of moderate to severe upper limb tremor in 20 patients with ET and 22 patients with PT were used to quantitatively compare tremor amplitude, frequency and pattern of muscle bursting in two resting and three non resting postures. The group statistics showed significant differences between ET and PT with respect to tremor frequency in all five postures, tremor amplitude at rest and muscle bursting patterns. Discriminant function analysis showed that no single parameter or combination of parameters was able to correctly classify all patients. Frequency was much more discriminating than amplitude or muscle bursting patterns in all limb postures. The best amplitude discrimination was obtained when the hand and forearm were both fully supported. Muscle bursting patterns were poorly discriminating and did not assist in correct classification of single patients. Group statistics confirmed a highly significant biological difference between the two tremor types. Optimal classification of single PT (86% correct) and ET (95% correct) patients was obtained using frequency and two selected amplitude parameters from the resting limb. Limb posture was an important variable in optimising the discriminative ability of tremor studies. The implications for routine tremor studies are summarised.

Lesion of thalamic centromedian--parafascicular complex after chronic deep brain stimulation.

A patient with PD who exhibited disabling tremor and prominent dyskinesia underwent deep brain stimulation (DBS) of the left thalamic ventral intermediate nucleus. The electrode migrated and was replaced but with suboptimal clinical response. Two years later, postmortem analysis found the second electrode tip had entered the thalamic centromedian-parafascicular complex. There was a small thalamotomy and cell loss exceeding that found in PD. Thalamic damage may occur in association with DBS for PD.

Activity of the leukocyte NADPH oxidase in whole neutrophils and cell-free neutrophil preparations stimulated with long-chain polyunsaturated fatty acids.

Fish oils are known for their anti-inflammatory effects. In this paper we investigated the influence of eicosapentaenoic acid and docosahexaenoic acid (omega-3 fatty acids), as well as docosapentaenoic acid, a metabolic product of omega-3 fatty acid metabolism, on O2(-)-production catalyzed by the NADPH oxidase in whole neutrophils and in a cell-free system consisting of neutrophil membranes and cytosol. As a standard we used arachidonic acid (an omega-6 fatty acid) found in a high proportion in the Western diet, and known as an effective activator of the oxidase in both systems. Our data show that with omega-3 fatty acids, the O2(-)-production in both systems is reduced as compared to the effect of arachidonic acid. The effects are more pronounced with increasing carbon chain length and increasing numbers of double bonds. Our results suggest another mechanism besides the inhibition of eicosanoid and cytokine production to explain the beneficial effects of fish oils in reducing inflammation.

A dissociation between subjective and objective unsteadiness in primary orthostatic tremor.

Patients with primary orthostatic tremor (OT) experience a disabling sense of unsteadiness but rarely fall. In order to study the relationship between the development of subjective unsteadiness, objective unsteadiness and tremor, we recorded standing under four conditions (eyes open or closed, feet together or apart) in six patients with OT. Subjective unsteadiness was indicated by the patients on a four-point scale using a hand-held slider. Objective unsteadiness was assessed by measuring the path lengths of the centre of foot pressure and body motion at the level of the cervical spine. Tremor was measured by surface electromyography from leg and paraspinal muscles. OT patients were objectively more unsteady than controls. Objective unsteadiness also increased disproportionately in patients when standing with eyes closed. These findings suggest that balance control in OT is abnormal and shows increased visual dependence. Subjective unsteadiness increased from mild to severe over seconds to minutes. The increase was faster when standing with eyes closed or feet together. However, although escalating subjective unsteadiness was paralleled by an increase in leg tremor, there were no comparable changes in either paraspinal tremor or objective unsteadiness during the course of a stand. We conclude that there is a dissociation between subjective and objective unsteadiness. This implies that subjective unsteadiness does not arise simply from an awareness of increased body sway. We postulate that the sensation of unsteadiness arises from a tremulous disruption of proprioceptive afferent activity from the legs. This disturbance gives rise to increased co-contracting drive to the leg muscles in order to stiffen the joints and increase stability. Since muscle activity remains tremor-locked, the tremulous proprioceptive feedback is increased, which then further increases the sensation of unsteadiness, and so on in a vicious circle of escalating activity.

Treatment of Parkinson's disease.

The aim of current treatment of Parkinson's disease is to ameliorate the symptoms while seeking to lessen the potential development of late levodopa complications. To this end, there is ample evidence that the early use of dopamine agonists is beneficial in younger Parkinsonian patients but monotherapy with dopamine agonists is for only a select few. Nonergot dopamine agonists offer the potential for fewer side effects. Lower dose levodopa therapy delays the onset and reduces severity of dyskinesia and end of dose failure. However levodopa remains the treatment of choice in Parkinson's disease and should not be restricted unnecessarily in patients with disability. There is no evidence that levodopa is toxic to dopaminergic neurons in people with Parkinson's disease. As yet, no drugs are of proven neuroprotective value. Dopamine agonists, catechol-o-methyltransferase inhibitors, amantadine and apomorphine have differing but beneficial roles in the management of levodopa side effects. Ablative surgery and deep brain stimulation of thalamus, globus pallidus and subthalamic nucleus are increasingly available but choice of procedure depends not just on patient symptomatology, but also on local experience and results. Ideally, deep brain stimulation is the treatment of choice as it offers less morbidity than bilateral ablative surgery, the possibility of postoperative adjustments and the potential for reversibility if better treatments become available.