Drug-Induced Movement Disorders.

Drug-induced movement disorders (DIMDs) are most commonly associated with typical and atypical antipsychotics. However, other drugs such as antidepressants, antihistamines, antiepileptics, antiarrhythmics, and gastrointestinal drugs can also cause abnormal involuntary movements. Different types of movement disorders can also occur because of adverse drug reactions. Therefore, the important key to diagnosing DIMDs is a causal relationship between potential offending drugs and the occurrence of abnormal movements. The pathophysiology of DIMDs is not clearly understood; however, many cases of DIMDs are thought to exert adverse mechanisms of action in the basal ganglia. The treatment of some DIMDs is quite challenging, and removing the offending drugs may not be possible in some conditions such as withdrawing antipsychotics in the patient with partially or uncontrollable neuropsychiatric conditions. Future research is needed to understand the mechanism of DIMDs and the development of drugs with better side-effect profiles. This article reviews the phenomenology, diagnostic criteria, pathophysiology, and management of DIMDs.

Parkinsonian syndromes: A review.

Since James Parkinson published his remarkable clinical observations in the "An Essay On The Shaking Palsy" in 1817, the number of diseases included in the spectrum of parkinsonian syndromes (a group of diseases that have some part of their clinical features resembling those seen in Parkinson's disease), are growing. Careful history taking, comprehensive neurological examination, and utilization of proper investigations will lead the physicians to make an accurate diagnosis of the specific disease entity present. In this recent review, we cover the issue of classification of parkinsonian syndromes, and comprehensively review the characteristic features of the commonly encountered diseases that present with this syndrome. The salient aspects of the epidemiology, key clinical features, proper investigations, and possible treatment options of these diseases have also been addressed.

Prevalence of Thai patients with advanced Parkinson's disease and external validation of the 5-2-1 Criteria and the CDEPA Questionnaire: A single-centered, cross-sectional study.

BACKGROUND: Advanced stage of Parkinson's disease (APD) diagnosis is challenging for general neurologists. The 5-2-1 Criteria and the Cuestionario De Enfermedad de Parkinson Avanzada (CDEPA) have been validated for screening for APD. OBJECTIVE: This article reports the period-prevalence of APD defined by a movement disorder expert, the 5-2-1 Criteria, and CDEPA and to improve the screening performance of the 5-2-1 Criteria METHODS: A cross-sectional retrospective study at the Parkinson's disease (PD) clinic of a tertiary hospital in Bangkok, Thailand amongst all PD patients aged ≥ 18 years was performed from January 2016 to January 2020. We compared the characteristics of APD and non-APD patients. We externally validated the 5-2-1 Criteria and CDEPA. We explored improving the 5-2-1 Criteria. RESULTS: Of 480 PD patients with complete data, the period-prevalence of APD by the movement disorder expert, the 5-2-1 Criteria and CDEPA were 37.1 %, 48.5 %, and 27.5 %, respectively. Adding requiring help with an activity of daily living and freezing of gait to the original 5-2-1 Criteria enhanced the sensitivity from 86.5 % (95 %CI 80.6, 91.2) to 94.9 % (95 %CI 90.6, 97.7) and negative predictive value (NPV) from 90.3 % (95 %CI 85.9, 93.7) to 96 % (95 %CI 92.6, 98.2). However, the CDEPA had a sensitivity of 62.9 % (95 %CI 55.4, 70) and NPV of 81.0 (95 %CI 76.5, 85). CONCLUSION: The 5-2-1 Criteria had a good screening tool performance for general neurologists to refer APD patients for optimal treatments. The modified 5-2-1 Criteria had better performance than the original one. External validation is needed.

Validity and Reliability of the Thai Version of the Freezing of Gait Questionnaire in Individuals With Parkinson's disease.

OBJECTIVE: To evaluate the validity and reliability of the Thai version of the Freezing of Gait Questionnaire (FOG-Q) in individuals with Parkinson's disease (PD). METHODS: The FOG-Q was translated into Thai according to the standard process. Fifty-six individuals with PD participated in the study. The content validity was assessed using the content validity index (CVI). The construct validity was evaluated by correlating Thai FOG-Q with Thai version of the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) items 2.13 and 3.11, Thai version of the Falls Efficacy Scale-International (FES-I), Timed Up and Go test (TUG) and Berg Balance Scale (BBS) using Spearman's correlation coefficient (rS). The correlation between Thai FOG-Q and clinical characteristics, for example, duration of PD and modified Hoehn and Yahr (mH&Y) stage was evaluated. Internal consistency and test-retest reliability were evaluated with Cronbach's alpha (Cα) and intraclass correlation coefficient (ICC), respectively. RESULTS: The Thai FOG-Q had high content validity (CVI=0.96). The mean FOG-Q score was 9.0±4.9. The construct validity showed a strong positive correlation with MDS-UPDRS item 2.13 (rS=0.81), and moderate correlations with MDS-UPDRS item 3.11, FES-I, and TUG (rS=0.42-0.60). A negative correlation with BBS was found (rS=-0.32). It had a moderate correlation with mH&Y stage (rS=0.40). The Thai FOG-Q had good internal consistency (Cα=0.87) with excellent test-retest reliability (ICC=0.91). CONCLUSION: The Thai FOG-Q has excellent validity and reliability. It is a useful instrument for the evaluation of FOG in individuals with PD.

Movement Disorders and Musculoskeletal System: A Reciprocal Relationship.

The association of movement disorders (MDs) with musculoskeletal (MSK) disorders is observed in two principal scenarios. First, MDs patients may present with MSK issues. This phenomenon is primarily observed in parkinsonian syndromes, but may also be seen in patients with dystonia, Tourette syndrome, and some gene-related MDs. Second, there are MSK disorders that may produce or mimic MDs. Important primary MSK disorders producing MDs are joint hyperlaxity syndrome, non-traumatic craniovertebral junction anomalies, congenital muscular torticollis, and rheumatoid arthritis. Peripheral trauma to the MSK system may also lead to MDs commonly referred to as peripherally induced MDs. The exact pathogenesis of these disorders is not clear, however many patients have associated sensory phenomena such as complex regional pain syndrome. Herein, we provide an overview of disorders that may manifest with a combination of MSK and MDs, as detailed above. The most common MDs are discussed in each section, along with important clinical points, suggested diagnostic workups, and possible differential diagnoses.

Validation of the Thai Version of the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale.

OBJECTIVE: This study aims to validate the Thai translation of the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS). METHODS: The English version was translated into Thai and then back-translated into English. The translated version underwent 2 rounds of cognitive pretesting to assess the ease of comprehension, ease of use and comfort with the scale. Then, it underwent large clinimetric testing. RESULTS: The Thai version was validated in 354 PD patients. The comparative fit index (CFI) for all four parts of the Thai version of the MDS-UPDRS was 0.93 or greater. Exploratory factor analysis identified isolated item differences in factor structure between the Thai and English versions. CONCLUSION: The overall factor structure of the Thai version was consistent with that of the English version based on the high CFIs (all CFI ≥ 0.90). Hence, it can be designated the official Thai version of the MDS-UPDRS.

Gait and axial postural abnormalities correlations in Parkinson's disease: A multicenter quantitative study.

INTRODUCTION: Gait and axial postural abnormalities (PA) are common and disabling symptoms of Parkinson's disease (PD). The interplay between them has been poorly explored. METHODS: A standardized protocol encompassing videos and photos for posture and gait analysis of PD patients with a clinically defined PA (MDS-UPDRS-III item 3.13 > 0) was used in 6 movement disorder centers. A comprehensive evaluation was performed to clarify the association between gait performance and the presence and severity of PA. RESULTS: 225 PD patients were enrolled: 57 had severe PA, 149 mild PA, and 19 did not meet criteria for PA, according to a recent consensus agreement on PA definition. PD patients with severe PA were significantly older (p:0.001), with longer disease duration (p:0.007), worse MDS-UPDRS-II and -III scores and axial sub-scores (p < 0.0005), higher LEDD (p:0.002) and HY stage (p < 0.0005), and a significantly lower velocity (p < 0.001) and cadence (p:0.021), if compared to mild PA patients. The multiple regression analysis evaluating gait parameters and degrees of trunk/neck flexion showed that higher degrees of lumbar anterior trunk flexion were correlated with lower step length (OR -0.244; p:0.014) and lower velocity (OR -0.005; p:0.028). CONCLUSIONS: Our results highlight the possible impact of severe anterior trunk flection on PD patients' gait, with a specific detrimental effect on gait velocity and step length. Personalized rehabilitation strategies should be elaborated based on the different features of PA, aiming to target a combined treatment of postural and specifically related gait pattern alterations.

Postural abnormalities in Asian and Caucasian Parkinson's disease patients: A multicenter study.

INTRODUCTION: Postural abnormalities (PA) are disabling features of Parkinson's disease (PD). Indirect analyses suggested a higher prevalence of PA among Asian patients compared to Caucasian ones, but no direct comparisons have been performed so far. METHODS: An international, multicenter, cross-sectional study was performed in 6 European and Asian movement disorders centers with the aim to clarify differences and similarities of prevalence and characteristics of PA in Asian vs. Caucasian PD patients. Axial PA, encompassing antecollis (AC), camptocormia (CC), and Pisa syndrome (PS), and appendicular PA (appPA) were systematically searched and analysed in consecutive patients. RESULTS: 88 (27%) of 326 PD patients had PA (29.1% in Asians and 24.3% in Caucasians, p: 0.331). Prevalence of axial PA was 23.6% in Asians and 24.3% in Caucasians (p = 0.886), in spite of a longer disease duration among Caucasians, but a longer PA duration among Asians. No differences in prevalence between AC, CC, and PS were found between the two ethnicities. The prevalence of appPA was higher in Asians (p = 0.036), but the regression analysis did not confirm a significant difference related to ethnicity. Considering the whole population, male gender (OR, 4.036; 95% CI, 1.926-8.456; p < 0.005), a longer disease duration (OR, 2.61; 95% CI, 1.024-6.653; p = 0.044), and a higher axial score (OR, 1.242; 95% CI, 1.122-1.375; p < 0.0005) were the factors associated with axial PA. CONCLUSION: The prevalence of axial PA in PD patients is not influenced by ethnicity. However, Asian PD patients tend to develop PA earlier in the disease course, particularly AC.

Rhabdomyolysis Associated with Severe Levodopa-Induced Dyskinesia in Parkinson's Disease: A Report of Two Cases and Literature Review.

Background: Rhabdomyolysis associated with levodopa-induced dyskinesia (Rhab-LID) is an extremely rare, life-threatening, but treatable condition in patients with Parkinson's disease (PD). Case report: We reported two cases of Rhab-LID. The first case was a 64-year-old man presenting with severe generalized dyskinesia with elevated serum creatine kinase (CK) level. He was diagnosed with Rhab-LID owing to unpredictable gastric emptying time. The second case was a 61-year-old woman presenting with fever, myalgia, and disabling dyskinesia with elevated serum CK. She was diagnosed with dyskinesia-hyperpyrexia syndrome (DHS) due to increasing dosage of ropinirole and infection. Dopaminergic medications were stopped, and supportive care was initiated in both cases with excellent outcomes. Conclusion: Early recognition, stopping dopaminergic medications, treating precipitating causes, and proper supportive treatment can provide favorable outcomes.

The association between developing Parkinson's disease and ß-Adrenoceptor acting agents use: A systematic review and meta-analysis.

INTRODUCTION: Parkinson's disease (PD) ranks the second most common neurodegenerative disease. Aside from genetic predisposition, many external factors such as traumatic brain injury and exposure of substances including pesticides also contribute to PD's pathogenesis. Many previous studies observed the association between the use of ß-adrenoceptor acting agents and risk of PD. OBJECTIVE: To conduct systematic review and meta-analysis to summarize whether the use of ß-agonist and ß-antagonist agents were associated with risk of PD. METHOD: We independently searched for published studies from EMBASE and MEDLINE databases from inception to February 2021. This meta-analysis includes 9 case-control studies and 1 cohort study meeting the eligibility criteria, with a total of 380,105 participants. RESULTS: Overall ß-antagonists use appeared to associate with increase PD risk with an odd ratio (OR) of 1.2 (95% CI 1.07-1.34). Propranolol and metoprolol had a statistically significant association with higher risk of PD: pooled OR was 1.67 (95% CI 1.22-2.29) and 1.07 (95% CI 1.03-1.1), respectively. On the other hand, ß-agonists significantly inverse association with PD risk with OR of 0.88 (95% CI 0.85-0.92). Salbutamol unexpectedly showed no statistical significance in reduced risk of PD with a pooled risk ratio of 1.0 (95% CI 0.87-1.16). CONCLUSION: Overall ß-antagonists, including propranolol and metoprolol, were associated with an increased risk of PD, in contrast to ß-agonists, which were associated with decreased the risk.

Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) in a Thai Patient: The Classic Clinical Manifestations, Funduscopic Feature, and Brain Imaging Findings with a Novel Mutation in the SACS Gene.

Background: A 38-year-old woman was diagnosed autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) with a novel pathogenic variant in the SACS gene presented with gradually progressive spastic ataxia since the age of 2 years; then, she became wheelchair-bound at the age of 28 years. Phenomenology: The patient presented a combination of cerebellar dysfunctions e.g., gaze-evoked nystagmus, scanning speech, finger dysmetria, and wide-based gait, lower limb spasticity, and typical funduscopic examination which was a hypermyelinated nerve fibers radiating from the optic disc. Educational value: At present, ARSACS is recognized as a rare, worldwide, inherited movement disorder in which we should to aware of a diagnosis of this disorder in the patient who is presented with FXN gene negative early-onset spastic ataxia.

Facio-Oculo-Palatal Myoclonus Complicated by a Recurrent Brainstem Stroke.

Background: A 54-year-old Thai male who has suffered from multiple episodes of ischemic and hemorrhagic strokes developed facio-oculo-palatal myoclonus (FOPM) 1 month after the latest episode of the brainstem stroke. Phenomenology Shown: The patient presented with semirhythmic, involuntary, horizontal jerky, and rotatory ocular oscillation concomitant with asymmetrical palatal and perioral myoclonus consistent with FOPM. Educational value: FOPM is a useful clinical clue for diagnosing brainstem lesions, specifically in the Guillain-Mollaret triangle. The commonest etiology is cerebrovascular diseases.

Steroid-responsive Encephalopathy Associated with Autoimmune Thyroiditis (SREAT) Presenting with Pure Cerebellar Ataxia.

Background: Myoclonus and tremor are common movement disorder phenomenologies in steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT). Pure ataxia without encephalopathy has rarely been reported. Case report: We report 21- and 40-year-old females who presented with subacute pure ataxia without encephalopathy. After immunotherapies, both exhibited initial improvement of ataxia, and subsequently remained in plateau phase. Discussion: This treatable disorder should be added to the differential diagnoses of progressive cerebellar ataxia, and anti-thyroid peroxidase and anti-thyroglobulin should be considered as part of the workup. It is crucial not to misdiagnose SREAT presenting with pure cerebellar ataxia as degenerative or spinocerebellar ataxia.

Brainstem dysfunction heralding disseminated cryptococcosis.

Cryptococcal meningoencephalitis is one of the most common central nervous system infections affecting immunocompromised patients. However, brainstem involvement is extremely rare and may represent a diagnostic challenge to clinicians. We report a non-HIV infected, chronically immunosuppressed, patient with fatal disseminated cryptococcosis presented with subcutaneous masses at both thighs and progressive brainstem dysfunction. Magnetic resonance imaging demonstrated multiple brainstem infarcts likely derived from small vessel vasculopathy. Anti-fungal treatment led to partial neurologic improvement but the patient succumbed to a fatal sepsis from hospital-acquired pneumonia.