The impact of Tai Chi and Qigong mind-body exercises on motor and non-motor function and quality of life in Parkinson's disease: A systematic review and meta-analysis.

PURPOSE: To systematically evaluate and quantify the effects of Tai Chi/Qigong (TCQ) on motor (UPDRS III, balance, falls, Timed-Up-and-Go, and 6-Minute Walk) and non-motor (depression and cognition) function, and quality of life (QOL) in patients with Parkinson's disease (PD). METHODS: A systematic search in 7 electronic databases targeted clinical studies evaluating TCQ for individuals with PD published through August 2016. Meta-analysis was used to estimate effect sizes (Hedges's g) and publication bias for randomized controlled trials (RCTs). Methodological bias in RCTs was assessed by two raters. RESULTS: Our search identified 21 studies, 15 of which were RCTs with a total of 735 subjects. For RCTs, comparison groups included no treatment (n = 7, 47%) and active interventions (n = 8, 53%). Duration of TCQ ranged from 2 to 6 months. Methodological bias was low in 6 studies, moderate in 7, and high in 2. Fixed-effect models showed that TCQ was associated with significant improvement on most motor outcomes (UPDRS III [ES = -0.444, p < 0.001], balance [ES = 0.544, p < 0.001], Timed-Up-and-Go [ES = -0.341, p = 0.005], 6 MW [ES = -0.293, p = 0.06], falls [ES = -0.403, p = 0.004], as well as depression [ES = -0.457, p = 0.008] and QOL [ES = -0.393, p < 0.001], but not cognition [ES = -0.225, p = 0.477]). I2 indicated limited heterogeneity. Funnel plots suggested some degree of publication bias. CONCLUSION: Evidence to date supports a potential benefit of TCQ for improving motor function, depression and QOL for individuals with PD, and validates the need for additional large-scale trials.

Fall frequency and risk assessment in early Parkinson's disease.

BACKGROUND: We sought to define the frequency of falls in early PD and assess potential risk factors for falls in this population. METHODS: We analyzed the data from two randomized, placebo controlled trials (NET-PD FS1 and FS-TOO) of 413 individuals with early PD over 18 months of follow-up in FS1 and 12 months in FS-TOO. Falls were defined as any report of falls on the UPDRS or the adverse event log. We assessed the frequency of falls overall and by age. The relationship between prespecified fall risk markers and the probability of falling was assessed using logistic and multiple logistic regression. A hurdle Poisson model was used to jointly model the probability of remaining fall-free and the number of falls. RESULTS: During the follow-up period, 23% of participants fell, and 11% were habitual fallers. In a multiple logistic regression model, age, baseline UPDRS Falling score, and baseline PDQ-39 scores were associated with subsequent fall risk (p < 0.001). Similarly, in a hurdle Poisson regression model, age, baseline UPDRS falling item, and baseline PDQ-39 were all significantly related to the probability of falling, but only UPDRS falling >0 was associated with the number of falls. CONCLUSION: Falls are frequent and are associated with impaired quality of life, even in early PD. Current standard rating scales do not sufficiently explain future fall risk in the absence of a prior fall history. New assessment methods for falls and postural instability are required to better evaluate this important problem in clinical trials and clinical practice.

Laserlight cues for gait freezing in Parkinson's disease: an open-label study.

Freezing of gait (FOG) and falls are major sources of disability for Parkinson's disease (PD) patients, and show limited responsiveness to medications. We assessed the efficacy of visual cues for overcoming FOG in an open-label study of 26 patients with PD. The change in the frequency of falls was a secondary outcome measure. Subjects underwent a 1-2 month baseline period of use of a cane or walker without visual cues, followed by 1 month using the same device with the laserlight visual cue. The laserlight visual cue was associated with a modest but significant mean reduction in FOG Questionnaire (FOGQ) scores of 1.25 ± 0.48 (p = 0.0152, two-tailed paired t-test), representing a 6.6% improvement compared to the mean baseline FOGQ scores of 18.8. The mean reduction in fall frequency was 39.5 ± 9.3% with the laserlight visual cue among subjects experiencing at least one fall during the baseline and subsequent study periods (p = 0.002; two-tailed one-sample t-test with hypothesized mean of 0). Though some individual subjects may have benefited, the overall mean performance on the timed gait test (TGT) across all subjects did not significantly change. However, among the 4 subjects who underwent repeated testing of the TGT, one showed a 50% mean improvement in TGT performance with the laserlight visual cue (p = 0.005; two-tailed paired t-test). This open-label study provides evidence for modest efficacy of a laserlight visual cue in overcoming FOG and reducing falls in PD patients.

Experience with transumbilical breast augmentation.

Transumbilical breast augmentation (TUBA), an endoscopicassisted procedure in which saline breast prostheses are inserted through the umbilicus, is a patient-driven, frequently performed procedure that remains controversial. The author describes the operative technique and results in 90 patients who underwent TUBA between October 1996 and July 2000 by the same surgeon in a community practice. A total of 85 patients underwent submammary TUBA and 5 patients underwent submuscular TUBA. Seventy patients were available for follow-up. Postoperative results of the 70 patients were graded as very good in 56 (80%), good in 12 (17%), and fair in 2 (2.9%). Complications were conversion to an open approach in 1 patient and an accidental submuscular entry into the pocket in 1 patient. There were four capsular contractures (5.7%), 5 patients (7.1%) were reoperated: 2 for capsulectomies, 1 for implant buckling, 1 for scar revision, and 1 for removal of the implants. There were no implant ruptures, hematomas, or infections. Advantages of TUBA include minimal scarring, remote incision, short operating time, low capsular contracture rate, and rapid recovery. These results of this evolving procedure suggest that in select patients TUBA provides a high level of patient satisfaction and low complication rates. As TUBA techniques for submuscular placement continue to develop, more patients may become TUBA candidates.

Neurologic disorders of gait.

Gait disorders are important because of their prevalence, particularly among the elderly, and the associated risk of falls and injury. Neural networks that organize locomotion and maintain balance are briefly reviewed. Gait disorders can be classified based on observational features or by etiology. Several common disorders are discussed in more detail. Recent progress includes use of botulinum toxin for spastic gait in cerebral palsy, neurosurgical treatment of Parkinson's disease, and newer rehabilitation approaches to gait and balance training.

Dystonia as a presenting feature of the 3243 mitochondrial DNA mutation.

A variety of neurologic phenotypes have been described in patients with mitochondrial disorders. We report a 32-year-old man in whom dystonia was the salient and presenting feature of a mitochondrial DNA mutation. He presented at age 23 with writer's cramp and progressed over 5 years to exhibit dystonia in facial muscles and lower limbs. He also has exercise intolerance, mild, bilateral ptosis, proximal muscle weakness, and sensorineural hearing loss. Molecular genetic analysis of blood, urine, and muscle biopsy demonstrated the presence of a heteroplasmic point mutation at nucleotide position 3243. The 3243 mtDNA mutation has pleomorphic manifestations, and dystonia should be added to the list of associated clinical features.

Treatment of occupational cramp with botulinum toxin: diffusion of toxin to adjacent noninjected muscles.

Over a 5-year period, 40 patients, 11 with musician's and 29 with writer's cramp, were treated with botulinum toxin A using a precise injection technique in which the hollow-bore electromyography (EMG) needle was positioned by both standard EMG and by muscle twitch evoked by stimulating current passed through it. Moderate to complete improvement in dystonia occurred in 28 patients (70%) after the first injection and in 34 patients (85%) after the second injection with better outcome in nonmusicians than in musicians. Of note, weakness of uninjected muscles, immediately adjacent to those injected, was found in 25/40 patients (63%). The most common patterns of toxin spread were from flexor digitorum sublimis to profundus, extensor carpi radialis to extensor digitorum communis, and extensor indicis proprius to extensor pollicis brevis. Spread to, and weakness of, adjacent uninjected muscles was a major factor contributing to suboptimal outcome in 6/39 (15%) such patients.

A familial factor independent of CAG repeat length influences age at onset of Machado-Joseph disease.

Machado-Joseph disease (MJD) is a late-onset, progressive, neurodegenerative disorder caused by the expansion of an unstable trinucleotide (CAG) repeat sequence in a novel gene (MJD1) on chromosome 14. Previous studies showed that age at onset is negatively correlated with the number of CAG repeat units, but only part of the variation in onset age is explained by CAG repeat length. Ages at onset and CAG repeat lengths of 136 MJD patients from 23 kindreds of Portuguese descent were analyzed, to determine whether familial factors independent of CAG repeat length modulate age at onset of MJD. Correlation among sibs for onset age adjusted for CAG repeat length was .43, which indicates that an environmental or genetic factor common to sibs influences onset age. Positive correlations were also observed for avuncular (r = .22) and first-cousin pairs (r = .28), which supports the hypothesis that a genetic factor is influencing age at onset. Commingling analysis of onset ages adjusted for CAG repeat length identified three distributions in this population of affected individuals. Further studies of a much larger sample are needed to determine whether these distributions represent the influence of a genetic or environmental factor.

Frequency of spinocerebellar ataxia type 1, dentatorubropallidoluysian atrophy, and Machado-Joseph disease mutations in a large group of spinocerebellar ataxia patients.

The spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative disorders varying in both clinical manifestations and mode of inheritance. Six different genes causing autosomal dominant SCA are mapped: SCA1, SCA2, Machado-Joseph disease (MJD)/SCA3, SCA4, SCA5, and dentatorubropallidoluysian atrophy (DRPLA). Expansions of an unstable trinucleotide CAG repeat cause three of these disorders: SCA type 1 (SCA1), MJD, and DRPLA. We determine the frequency of the SCA1, DRPLA, and MJD mutations in a large group of unrelated SCA patients with various patterns of inheritance and different ethnic backgrounds. We studied 92 unrelated SCA patients. The frequency of the SCA1 mutation was 3% in the overall patient group and 10% in the non-Portuguese dominantly inherited SCA subgroup. We found that DRPLA mutation in only one Japanese patient, who was previously diagnosed with this disease. We identified the MJD mutation in 41% of the overall patient group, which included 38 autosomal dominant kindreds of Portuguese origin; the frequency of the MJD mutation among the non-Portuguese dominantly inherited cases was 17%. These results suggest that SCA may be occasionally caused by the SCA1 mutation and rarely caused by the DRPLA mutation and that, to date, the MJD mutation seems to be the most common cause of dominantly inherited SCA. Finally, our results suggest that recessively inherited cases of SCA are not caused by the known trinucleotide repeat expansions.

Correlation between CAG repeat length and clinical features in Machado-Joseph disease.

Machado-Joseph disease (MJD) is associated with the expansion of a CAG trinucleotide repeat in a novel gene on 14q32.1. We confirmed the presence of this expansion in 156 MJD patients from 33 families of different geographic origins: 15 Portuguese Azorean, 2 Brazilian, and 16 North American of Portuguese Azorean descent. Normal chromosomes contain between 12 and 37 CAG repeats in the MJD gene, whereas MJD gene carriers have alleles within the expanded range of 62-84 CAG units. The distribution of expanded alleles and the gap between normal and expanded allele sizes is either inconsistent with a premutation hypothesis or most (if not all) of the alleles we studied descend from a common ancestor. There is a strong correlation between the expanded repeat size and the age at onset of the disease as well as the clinical presentation. There is mild instability of the CAG tract length with transmission of the expanded alleles; both increase and decrease in size between parents and progeny occur, with larger variations in male than in female transmissions. Together, these effects can partly explain the variability of age at onset and of phenotypic features in MJD; however, other modifying factors must exist.

Machado-Joseph disease.

Machado-Joseph disease (MJD) is a form of dominantly-inherited ataxia originally described in people of Azorean and Portuguese descent. The disorder has subsequently been identified in Japan, Brazil, Australia, and China. Average age of onset is 35 to 40. Core features include progressive ataxia, dysarthria, postural instability, nystagmus, eyelid retraction, and facial fasciculations. Dystonia is often prominent in younger patients. Three distinct phenotypes appear to reflect the clinical spectrum of a single mutant gene. Neuropathology involves afferent and efferent cerebellar systems, with preservation of cerebellar cortex and inferior olive. Spinocerebellar pathways, substantia nigra, and cranial nerve motor nuclei are involved. The disorder is due to an unstable CAG repeat on chromosome 14q32.1. A dominantly inherited ataxia (SCA-3) in families of French and German descent has also been linked to this segment of chromosome 14. The relationship between MJD and the other dominant inherited ataxias is discussed.

Treatment of stiff-man syndrome with intravenous immune globulin.

OBJECTIVE: To evaluate the efficacy of intravenous immune globulin (IVIG) in the treatment of stiff-man syndrome (SMS). METHODS: An open, unblinded study of 3 patients with active disease and/or disease refractory to treatment with diazepam and/or corticosteroids. RESULTS: All 3 bedridden patients improved substantially shortly after infusion with IVIG and regained function. CONCLUSION: IVIG may be useful for the treatment of SMS.

Limb dystonia following electrical injury.

Electrical injuries of the extremities may cause paralysis, muscle atrophy, sensory deficit, causalgia, and reflex sympathetic dystrophy (RSD). Limb dystonia has rarely been reported following electrical injury to an extremity, although it may result from cerebral hemisphere electrical trauma. Following electrical injury to the upper extremity, three patients developed limb dystonia accompanied by severe pain and sensory symptoms in two patients and features of RSD in one patient. Two patients received botulinum toxin injections without functional benefit. The mechanism of dystonia following peripheral trauma is unknown but may relate to reorganization of central synaptic connections, possibly in the spinal cord.

Machado-Joseph disease in New England: clinical description and distinction from the olivopontocerebellar atrophies.

Experience is described in 25 patients from southern New England with Machado-Joseph Disease, examined serially at annual screening clinics. The disorder is dominantly inherited, with a wide range of phenotypic variation. Core clinical features described include ataxia, nystagmus, dysarthria, facial fasciculations, and lid retraction, producing a characteristic staring expression. In addition, young onset patients have spasticity, extrapyramidal rigidity, and dystonic manifestations. Late onset patients often have distal atrophy and sensory loss. Postural instability is often an early feature. We discuss the distinction of this entity from the olivopontocerebellar atrophies.

Liquid crystal temperature monitoring for microsurgery.

Postoperative monitoring of free tissue transfers remains a problem for the microsurgeon. Liquid crystal temperature probes (LCT) are used by anesthesiologists to monitor patient core temperature and to indicate changes in temperature trends as an indicator of pending malignant hyperthermia. By placing an LCT monitor on the flap and adjacent tissue at the completion of surgery, temperature differentials can be reliably monitored. If the temperature differential exceeds 2 degrees C, the flap is re-explored. The LCT readout resembles a standard thermometer and can easily be recorded by even inexperienced personnel. LCTs are a convenient, inexpensive, and easy method to monitor both free muscle and free fasciocutaneous flaps.

Primary hyperparathyroidism associated with two enlarged parathyroid glands.

An increasingly recognized although small percentage of patients with primary hyperparathyroidism have enlargement of two parathyroid glands. We have treated nine patients with primary hyperparathyroidism associated with such double parathyroid gland enlargement. In four of these patients, marked asymmetry of the two enlarged glands was noted and the failure to recognize and excise a second enlarged parathyroid gland resulted in persistent or recurrent hyperparathyroidism. In one of these patients, the second enlargement was present in a super-numerary mediastinal gland. The subsequent excision of the second enlarged parathyroid gland resulted in normocalcemia in each instance. This contrasts with five patients in whom initial excision of two enlarged glands resulted in normocalcemia with no recurrence of hypercalcemia. Only three patients fulfilled the histologic criteria of true double adenomas. The remainder showed multiglandular hypercellularity. This experience supports identifying all parathyroid glands and recognizing that even minimal enlargement of a gland may be important pathophysiologically, regardless of its histopathologic classification. Excision of both enlarged glands, even if asymmetric, is appropriate.

The use of preoperative localization of adenomas of the parathyroid glands by thallium-technetium subtraction scintigraphy, high-resolution ultrasonography and computed tomography.

Thirty-six patients with primary hyperparathyroidism were studied preoperatively by thallium-201 and technetium-99m pertechnetate subtraction (Tl-201/Tc-99m) scintigraphy, high-resolution real time ultrasonography and computed tomographic (CT) scanning. None of the patients had had previous surgical treatment of the parathyroid or thyroid glands. All of the patients underwent systematic bilateral exploration of the neck. All of the patients were successfully explored and 41 abnormal parathyroid glands were identified. Five patients had two adenomas. In six instances, adenomas were identified in ectopic anatomic sites. The sensitivity of correctly localizing the abnormal glands with these techniques was 49 per cent for the Tl-201/Tc-99m scintigraphy, 34 per cent for ultrasonography and 41 per cent for CT scanning. The Tl-201/Tc-99m scintigrams detected two of the six ectopically located adenomas, CT detected one, while ultrasound detected none. The five patients with multiple adenomas were not accurately identified as having multiple gland enlargement by any of these studies. Therefore, preoperative localization studies with these three techniques did not provide reliable information for initial bilateral exploration of the neck.