A new therapeutic strategy with istradefylline for postural deformities in Parkinson's disease.

AIM OF THE STUDY: Postural deformities are common in Parkinson's disease (PD) patients. Several treatment options have been reported, but responses to these treatments appear unpredictable. Istradefylline is a novel drug for PD. Cases of PD patients whose postural deformities were improved after withdrawal of dopamine agonists and initiation of istradefylline are presented. MATERIALS AND METHODS: Four consecutive patients with postural deformities including antecollis, Pisa syndrome, and camptocormia were recruited and treated with istradefylline in combination with withdrawal of dopamine agonists, which are possible causes of postural deformities. RESULTS: The dopamine agonists were discontinued an average of 26 months after the development of the postural deformities, and istradefylline was initiated an average of 1.3 months after dopamine agonist withdrawal. Three patients with preserved paraspinal muscle volume showed good responses to the treatment regimen at least two months after dopamine agonist withdrawal. CONCLUSIONS AND CLINICAL IMPLICATIONS: Postural deformities caused by dopamine agonists generally improve less than two weeks after dopamine agonist withdrawal. Given the response time in the present study, the response was unlikely to be caused solely by dopamine agonist withdrawal. Istradefylline can be a potential therapeutic option; however, appropriate selection of patients for treatment with istradefylline is warranted.

Dropped Head Syndrome: The Importance of Neurophysiology in Distinguishing Myasthenia Gravis from Parkinson's Disease.

Dropped head syndrome (DHS) is characterized by severe forward flexion of the cervical spine due to an imbalance in neck muscle tone. This condition can be linked to various neuromuscular diseases, including myasthenia gravis (MG). On the other hand, Parkinson's disease (PD) patients may show a clinically indistinguishable picture named antecollis, which is caused by increased axial tone, but without muscle weakness. Differentiating between DHS and antecollis is crucial due to their distinct treatment requirements. We present the case of a 71-year-old White male with a one-month history of severe neck flexion, mild dysphagia, and dysphonia. His medical history included diabetes mellitus, coronary artery disease, arterial hypertension, and mild cervical spondylosis. Neurological examination revealed features of Parkinsonism, including hypomimia, asymmetric rigidity, and reduced arm swing. There was significant weakness in his neck extensor muscles, with no signs of ptosis or diplopia. Brain/spine MRI scans were unremarkable, but electromyography showed a reduced compound muscle action potentials amplitude in repetitive nerve stimulation, consistent with MG. High-titer acetylcholine receptor antibodies confirmed the diagnosis. Treatment with pyridostigmine (60 to 120 mg/day) and plasma exchange (daily, for five consecutive days) improved the patient's general condition and neck posture. Concurrently, the patient was diagnosed with PD based on established clinical criteria and improved with carbidopa/levodopa therapy (up to 150/600 mg/daily). This case highlights the rare co-occurrence of MG and PD, emphasizing the need for thorough clinical, neurophysiological, and laboratory evaluations in complex DHS presentations. Managing MG's life-threatening aspects and addressing PD symptoms requires a tailored approach, showcasing the critical role of neurophysiology in accurate diagnosis and effective treatment.

Significant improvement after sensory tricks and trunk strength training for Parkinson's disease with antecollis and camptocormia: A case report.

BACKGROUND: Patients with Parkinson's disease (PD) exhibit symptoms such as antecollis (AC) and camptocormia (CC). The pathology of these two conditions is unclear. Additionally, standard treatment methods have not been established. The article reports the case of a 65-year-old female patient with AC and CC who was treated with central and peripheral interventions to alleviate symptoms. CASE SUMMARY: We present the case of a 65-year-old female PD patient with AC and CC. The course of the disease was 5 years. She was treated with rehabilitation strategies such as sensory tricks and trunk strength training. During the inpatient period, we compared and analyzed the patient's gait, rehabilitation assessment scale score, and angles of her abnormal trunk posture in the first week, the third week, and the fifth week. The patient's stride length increased, indicating that the patient's walking ability was improved. The Unified Parkinson's Disease Scale Part Three score and CC severity score decreased. Furthermore, the score of the other scale increased. In addition, the patient showed significant improvements in AC, upper CC, and lower CC angles. CONCLUSION: This case study suggested that sensory tricks and trunk strength training are beneficial and safe for patients with AC and CC.

Predictors and Pathophysiology of Axial Postural Abnormalities in Parkinsonism: A Scoping Review.

Background: Postural abnormalities involving the trunk are referred to as axial postural abnormalities and can be observed in over 20% of patients with Parkinson's disease (PD) and in atypical parkinsonism. These symptoms are highly disabling and frequently associated with back pain and a worse quality of life in PD. Despite their frequency, little is known about the pathophysiology of these symptoms and scant data are reported about their clinical predictors, making it difficult to prompt prevention strategies. Objectives: We conducted a scoping literature review of clinical predictors and pathophysiology of axial postural abnormalities in patients with parkinsonism to identify key concepts, theories and evidence on this topic. Methods: We applied a systematic approach to identify studies, appraise quality of evidence, summarize main findings, and highlight knowledge gaps. Results: Ninety-two articles were reviewed: 25% reported on clinical predictors and 75% on pathophysiology. Most studies identified advanced disease stage and greater motor symptoms severity as independent clinical predictors in both PD and multiple system atrophy. Discrepant pathophysiology data suggested different potential central and peripheral pathogenic mechanisms. Conclusions: The recognition of clinical predictors and pathophysiology of axial postural abnormalities in parkinsonism is far from being elucidated due to literature bias, encompassing different inclusion criteria and measurement tools and heterogeneity of patient samples. Most studies identified advanced disease stage and higher burden of motor symptoms as possible clinical predictors. Pathophysiology data point toward many different (possibly non-mutually exclusive) mechanisms, including dystonia, rigidity, proprioceptive and vestibular impairment, and higher cognitive deficits.

Task Force Consensus on Nosology and Cut-Off Values for Axial Postural Abnormalities in Parkinsonism.

Background: There is no consensus with regard to the nosology and cut-off values for postural abnormalities in parkinsonism. Objective: To reach a consensus regarding the nosology and cut-off values. Methods: Using a modified Delphi panel method, multiple rounds of questionnaires were conducted by movement disorder experts to define nosology and cut-offs of postural abnormalities. Results: After separating axial from appendicular postural deformities, a full agreement was found for the following terms and cut-offs: camptocormia, with thoracic fulcrum (>45°) or lumbar fulcrum (>30°), Pisa syndrome (>10°), and antecollis (>45°). "Anterior trunk flexion," with thoracic (≥25° to ≤45°) or lumbar fulcrum (>15° to ≤30°), "lateral trunk flexion" (≥5° to ≤10°), and "anterior neck flexion" (>35° to ≤45°) were chosen for milder postural abnormalities. Conclusions: For axial postural abnormalities, we recommend the use of proposed cut-offs and six unique terms, namely camptocormia, Pisa syndrome, antecollis, anterior trunk flexion, lateral trunk flexion, anterior neck flexion, to harmonize clinical practice and future research.

Prevalence of and factors associated with postural deformities in Chinese patients with multiple system atrophy.

OBJECTIVE: The prevalence of postural deformities in patients with multiple system atrophy (MSA) has varied among previous studies. The objective of our study was to investigate the prevalence of and factors associated with postural deformities in Chinese MSA patients. METHODS: A total of 732 MSA patients were consecutively enrolled in the current study. Clinical data including age, sex, age of onset, disease duration, onset symptom and treatment were collected. The Unified Multiple System Atrophy Rating Scale (UMSARS) was used to evaluate the severity of the disease. RESULTS: One hundred and fourteen (15.6%) patients presented with camptocormia. Thirty-one (4.2%) patients manifested with Pisa syndrome. Twenty-four (3.3%) patients presented with antecollis. Patients who exhibited postural deformities were more common among the MSA patients with predominant parkinsonism (MSA-P) (P < 0.05). In addition, MSA patients with postural deformities had a longer disease duration compared to those patients without postural deformities (P < 0.001). After adjusting for disease duration, compared with patients without postural deformities, MSA patients with postural deformities presented with higher score of UMSARS-I (P < 0.001), UMSARS-II (P < 0.001), UMSARS-IV (P < 0.001), and total UMSARS (P < 0.001) scores. The binary logistic regression model indicated that the factors associated with postural deformity in MSA patients were the total UMSARS score (OR = 1.076, P < 0.001) and MSA-P subtype (OR = 3.870, P < 0.001). CONCLUSION: Postural deformities were common in Chinese MSA patients. Camptocormia was the most common type of postural deformity, followed by Pisa syndrome and antecollis. The factors associated with postural deformity were the severity of the disease and MSA-P subtype.

Etiology and Management of Spinal Deformity in Patients With Parkinson's Disease.

Patients with Parkinson's disease (PD) commonly develop severe spinal deformity, including scoliosis, antecollis, camptocormia, and Pisa syndrome. The etiology of PD-associated spinal deformity is not completely understood and in most cases is likely due to multiple interrelated factors, including central dystonia and focal myopathy. Once spinal deformity has occurred, surgery is often the only modality that can correct the condition, although control of the movement disorder through medication and deep brain stimulation may slow progression. Advances in spinal instrumentation and deformity correction techniques have improved the outcomes of PD spinal deformity patients, though complications and revision surgery rates remain high. Surgical intervention is reserved for individuals who are physiologically healthy and whose condition is refractory to nonoperative management and follows similar treatment principles as other causes of neuromuscular scoliosis/kyphosis. Spinal deformity patients with PD are optimally treated by spinal deformity surgeons who are familiar with the unique needs of PD patients, with vigilant preoperative and postoperative treatment of their movement disorder and bone density.

The adult motor phenotype of Dravet syndrome is associated with mutation of the STXBP1 gene and responds well to cannabidiol treatment.

Dravet syndrome is a terrible disease generally caused by mutations of the SCN1A gene. Recently others genes such as STXBP1 have been involved in the pathogenesis of the disease. The STXBP1 mutation in patients with Dravet Syndrome may additionally causes several parkinsonian features usually attributed to carriers of the SCN1A mutation. Management continues to be difficult that is why Cannabidiol emerged as valid option for treatment of this condition.

Can postural abnormality really respond to levodopa in Parkinson's disease?

OBJECTIVE: Abnormal postures affect motor function in Parkinson's disease (PD), potentially compromising the quality of life. The clinical efficacy of dopaminergic medications remains uncertain. Knowing what type of abnormal posture clearly responds to dopaminergic medication would facilitate the clinical management of PD. We investigated whether abnormal posture responded to dopamine challenge testing. METHODS: We studied 24 consecutive patients with PD who had anterior trunk flexion (ATF) (n=13), antecollis (n=4), or lateral trunk flexion (LTF) (n=7). Levodopa was infused intravenously over the course of 30min. Before and after the levodopa infusion, the angle of the posture was measured with the use of "Image J" software. RESULTS: After the infusion of levodopa, the angle of the overall abnormal posture significantly decreased (p<0.001). The angle of the abnormal posture significantly decreased in both natural position (p<0.001, p=0.002) and in a position with the back averted (p=0.003, p=0.029) in patients with ATF or antecollis, but did not change significantly in patients with LTF (p=0.099). The change in the angle differed significantly between patients with ATF and those with antecollis (p=0.017) and between patients with antecollis and those with LTF (p=0.008), but did not differ significantly between patients with ATF and those with LTF (p=0.052). The change in the angle in patients with abnormal posture related to the 'off' state was significantly greater than that in patients without abnormal posture related to the 'off' state (p<0.001). CONCLUSION: Patients with LTF and some patients with ATF poorly respond to levodopa. Two phenotypes of levodopa-responsiveness exist in patients with abnormal posture, and this observation is associated with an 'off' state, especially in patients with ATF.

Intrajejunal Infusion of Levodopa-Carbidopa Gel Can Continuously Reduce the Severity of Dropped Head in Parkinson's Disease.

Dropped head can occur in patients with Parkinson's disease and make their quality of life unpleasant because they cannot obtain a frontal view. The pathophysiologic involvement of dopamine agonist or central or peripheral mechanisms has been proposed. Levodopa therapy with the withdrawal of dopamine agonists was sometimes effective, but the effect in most patients did not persist for the entire day. We describe a patient with Parkinson's disease whose dropped head responded throughout the day to the continuous intrajejunal infusion of levodopa-carbidopa intestinal gel (LCIG). During off-periods before treatment with LCIG, severe akinesia and freezing of gait were evident, and she could not continuously obtain a frontal view because of the dropped head. About 20 min after the intrajejunal infusion of LCIG, these features remarkably improved, and she could obtain a frontal view. The angle of dropped head was improved from 39.39 to 14.04°. This case suggests that infusion of LCIG can reduce the severity of dropped head for a longer period than oral levodopa.