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Background Parkinson's disease is a common, progressive neurodegenerative disorder, the prevalence of which is on the rise. The diagnosis and management of Parkinson's disease is therefore likely to become increasingly frequent in general practice. Objective The aim of this article is to provide a practical overview for the general practitioner of the initial diagnosis and management of Parkinson's disease. Discussion Parkinson's disease is a multisystem disorder, and the way the diagnosis is delivered, as well as the early management, can have a lasting impact on the patient experience. In this article, the authors present their preferred approach to diagnosis and initial treatment, while highlighting common pitfalls and some useful simple strategies for communicating the diagnosis.

Introduction Dystonia is a clinically and genetically heterogeneous disorder and a genetic cause is often difficult to elucidate. This is the first study to use whole genome sequencing (WGS) to investigate dystonia in a large sample of affected individuals. Methods WGS was performed on 111 probands with heterogenous dystonia phenotypes. We performed analysis for coding and non-coding variants, copy number variants (CNVs), and structural variants (SVs). We assessed for an association between dystonia and 10 known dystonia risk variants. Results A genetic diagnosis was obtained for 11.7% (13/111) of individuals. We found that a genetic diagnosis was more likely in those with an earlier age at onset, younger age at testing, and a combined dystonia phenotype. We identified pathogenic/likely-pathogenic variants in ADCY5 (n = 1), ATM (n = 1), GNAL (n = 2), GLB1 (n = 1), KMT2B (n = 2), PRKN (n = 2), PRRT2 (n = 1), SGCE (n = 2), and THAP1 (n = 1). CNVs were detected in 3 individuals. We found an association between the known risk variant ARSG rs11655081 and dystonia (p = 0.003). Conclusion A genetic diagnosis was found in 11.7% of individuals with dystonia. The diagnostic yield was higher in those with an earlier age of onset, younger age at testing, and a combined dystonia phenotype. WGS may be particularly relevant for dystonia given that it allows for the detection of CNVs, which accounted for 23% of the genetically diagnosed cases.

The links between the two archetypical basal ganglia disorders, dystonia and parkinsonism, are manifold and stem from clinical observations, imaging studies, animal models and genetics. The combination of both, i.e. the syndrome of dystonia-parkinsonism, is not uncommonly seen in movement disorders clinics and has a myriad of different underlying aetiologies, upon which treatment and prognosis depend. Based on a comprehensive literature review, we delineate the clinical spectrum of disorders presenting with dystonia-parkinsonism. The clinical approach depends primarily on the age at onset, associated neurological or systemic symptoms and neuroimaging. The tempo of disease progression, and the response to L-dopa are further important clues to tailor diagnostic approaches that may encompass dopamine transporter imaging, CSF analysis and, last but not least, genetic testing. Later in life, sporadic neurodegenerative conditions are the most frequent cause, but the younger the patient, the more likely the cause is unravelled by the recent advances of molecular genetics that are focus of this review. Here, knowledge of the associated phenotypic spectrum is key to guide genetic testing and interpretation of test results. This article is part of the Special Issue "Parkinsonism across the spectrum of movement disorders and beyond" edited by Joseph Jankovic, Daniel D. Truong and Matteo Bologna.

Background Microscopic colitis is a form of inflammatory bowel disease characterized by profuse non-bloody watery diarrhea. Macroscopic abnormality is not present on colonoscopy, and it requires biopsy for diagnosis. Few cases have been attributed to levodopa/dopa-decarboxylase inhibitor therapy. Method A retrospective cohort study of 21 patients on levodopa/benserazide and one patient on levodopa-carbidopa intestinal gel with clinically suspected or biopsy proven microscopic colitis. Results All 21 patients on oral levodopa/benserazide had resolution of diarrhea with cessation of the medication. Four patients discontinued levodopa permanently. Two were rechallenged with levodopa/benserazide without symptom recurrence. One patient on oral levodopa/carbidopa developed diarrhea only with intermittent dispersible levodopa/benserazide. 14 were switched to levodopa/carbidopa with resolution of diarrhea in 9 but symptom recurrence in 5. One patient on oral levodopa/benserazide developed profuse diarrhea when switched to levodopa-carbidopa intestinal gel. Of 7/22 patients who had colonoscopy and biopsy, 5 had histopathological proven microscopic colitis. Conclusion levodopa/dopa-decarboxylase inhibitor induced microscopic colitis may be more common than previously suspected, with the potential to affect treatment compliance and therapeutic options.

Introduction In vivo dopamine transporter imaging is a useful tool for distinguishing nigrostriatal pathologies (e.g. Parkinson's disease) from other causes of tremor. However, while many of the motoric features of Parkinson's disease (e.g. bradykinesia, rigidity, hypomimia) correlate well with reduced striatal dopamine transporter binding, the same relationship has not been demonstrated for tremor. We investigated the relationship between striatal dopamine transporter binding and quantitative measures of tremor. Methods 23 participants with Parkinson's disease underwent standardised clinical assessment including structured, videotaped clinical examination, tremor neurophysiology study of both upper limbs using accelerometry and surface EMG, and Technitium-99 m TRODAT-1 brain SPECT imaging. Normalised striatal uptake values were calculated. Tremor EMG and accelerometry time series were processed with Fourier transformation to identify peak tremor power within a window of 3–10Hz and to calculate the tremor stability index (TSI). Results Spearman correlation analyses revealed an association between tremor power and contralaterally reduced striatal uptake in a number of recording conditions. This association was strongest for rest tremor, followed by postural tremor, with the weakest association observed for kinetic tremor. Lower TSI was also associated with lower contralateral striatal uptake in a number of rest and postural conditions. Conclusion These data suggest a relationship between Parkinsonian rest tremor and contralateral reduction in striatal dopamine binding. Use of quantitative neurophysiology techniques may allow the demonstration of clinico-pathophysiological relationships in tremor that have remained occult to previous studies.

Heterozygous mutations in KMT2B are associated with an early-onset, progressive and often complex dystonia (DYT28). Key characteristics of typical disease include focal motor features at disease presentation, evolving through a caudocranial pattern into generalized dystonia, with prominent oromandibular, laryngeal and cervical involvement. Although KMT2B-related disease is emerging as one of the most common causes of early-onset genetic dystonia, much remains to be understood about the full spectrum of the disease. We describe a cohort of 53 patients with KMT2B mutations, with detailed delineation of their clinical phenotype and molecular genetic features. We report new disease presentations, including atypical patterns of dystonia evolution and a subgroup of patients with a non-dystonic neurodevelopmental phenotype. In addition to the previously reported systemic features, our study has identified co-morbidities, including the risk of status dystonicus, intrauterine growth retardation, and endocrinopathies. Analysis of this study cohort (n = 53) in tandem with published cases (n = 80) revealed that patients with chromosomal deletions and protein truncating variants had a significantly higher burden of systemic disease (with earlier onset of dystonia) than those with missense variants. Eighteen individuals had detailed longitudinal data available after insertion of deep brain stimulation for medically refractory dystonia. Median age at deep brain stimulation was 11.5 years (range: 4.5–37.0 years). Follow-up after deep brain stimulation ranged from 0.25 to 22 years. Significant improvement of motor function and disability (as assessed by the Burke Fahn Marsden’s Dystonia Rating Scales, BFMDRS-M and BFMDRS-D) was evident at 6 months, 1 year and last follow-up (motor, P = 0.001, P = 0.004, and P = 0.012; disability, P = 0.009, P = 0.002 and P = 0.012). At 1 year post-deep brain stimulation, >50% of subjects showed BFMDRS-M and BFMDRS-D improvements of >30%. In the long-term deep brain stimulation cohort (deep brain stimulation inserted for >5 years, n = 8), improvement of >30% was maintained in 5/8 and 3/8 subjects for the BFMDRS-M and BFMDRS-D, respectively. The greatest BFMDRS-M improvements were observed for trunk (53.2%) and cervical (50.5%) dystonia, with less clinical impact on laryngeal dystonia. Improvements in gait dystonia decreased from 20.9% at 1 year to 16.2% at last assessment; no patient maintained a fully independent gait. Reduction of BFMDRS-D was maintained for swallowing (52.9%). Five patients developed mild parkinsonism following deep brain stimulation. KMT2B-related disease comprises an expanding continuum from infancy to adulthood, with early evidence of genotype-phenotype correlations. Except for laryngeal dysphonia, deep brain stimulation provides a significant improvement in quality of life and function with sustained clinical benefit depending on symptoms distribution.

Bobble-head doll syndrome (BHDS) is a rare entity, characterized by antero-posterior head bobbing, which is of the type "yes-yes." Less frequently, having a head movement of the type "no-no" is described. We report an unusual case of an 80-year-old man with a cystic mass of the lamina quadrigemina, extending to the posterior fossa. We conclude that ventriculocystocisternotomy associated with a cystoperitoneal shunt is an effective treatment for a symptomatic giant arachnoid cyst in the lamina quadrigemina.

A 49-year-old man developed cold intolerance as an isolated symptom 2 years prior to presentation. At age 48, he developed jerks in the trunk and lower limbs during the day and tapping movements in the arms during sleep. After 6 months, sleep disturbance worsened with talking and gesticulations, culminating in sleeping 1–3 hours per night with associated daytime somnolence. He developed mild slurred speech, hypersalivation, and dysphagia. He reported poor memory but was able to continue driving and working. He had been diagnosed with obstructive sleep apnea 4 years prior.

This review analyzes the bioecological model of human development as a comprehensive framework of adolescent antisocial behavior. Variables such as family and peers with antisocial backgrounds, antisocial peer attitudes, alcohol consumption, offensive behavior, education level, perception of safety in the community, and attention deficit hyperactive disorder, are discussed. This review supports the bioecological model as a plausible framework for understanding antisocial behavior during adolescence.

A 36-year-old man developed progressive limb pain, excessive sweating, and muscle cramps. He described transient strained voice only after drinking cold water (video 1). Examination revealed generalized myokymia and pseudomyotonia. EMG revealed multiple spontaneous, continuous high frequency doublet and triplet motor unit discharges. Nerve conduction studies and chest CT scan were normal. CASPR2 and LGI1 antibodies were negative. Autoimmune, paraneoplastic, and other etiologies were excluded clinically as well as through additional serologic (or blood) testing and imaging. Symptoms resolved completely after IV immunoglobulin and carbamazepine for treatment of pain.

Contains fulltext : 220616.pdf (Publisher’s version ) (Closed access) Genetic early-onset parkinsonism presenting from infancy to adolescence (≤21 years old) is a clinically diverse syndrome often combined with other hyperkinetic movement disorders, neurological and imaging abnormalities. The syndrome is genetically heterogeneous, with many causative genes already known. With the increased use of next-generation sequencing in clinical practice, there have been novel and unexpected insights into phenotype-genotype correlations and the discovery of new disease-causing genes. It is now recognized that mutations in a single gene can give rise to a broad phenotypic spectrum and that, conversely different genetic disorders can manifest with a similar phenotype. Accurate phenotypic characterization remains an essential step in interpreting genetic findings in undiagnosed patients. However, in the past decade, there has been a marked expansion in knowledge about the number of both disease-causing genes and phenotypic spectrum of early-onset cases. Detailed knowledge of genetic disorders and their clinical expression is required for rational planning of genetic and molecular testing, as well as correct interpretation of next-generation sequencing results. In this review we examine the relevant literature of genetic parkinsonism with ≤21 years onset, extracting data on associated movement disorders as well as other neurological and imaging features, to delineate syndromic patterns associated with early-onset parkinsonism. Excluding PRKN (parkin) mutations, >90% of the presenting phenotypes have a complex or atypical presentation, with dystonia, abnormal cognition, pyramidal signs, neuropsychiatric disorders, abnormal imaging and abnormal eye movements being the most common features. Furthermore, several imaging features and extraneurological manifestations are relatively specific for certain disorders and are important diagnostic clues. From the currently available literature, the most commonly implicated causes of early-onset parkinsonism have been elucidated but diagnosis is still challenging in many cases. Mutations in ∼70 different genes have been associated with early-onset parkinsonism or may feature parkinsonism as part of their phenotypic spectrum. Most of the cases are caused by recessively inherited mutations, followed by dominant and X-linked mutations, and rarely by mitochondrially inherited mutations. In infantile-onset parkinsonism, the phenotype of hypokinetic-rigid syndrome is most commonly caused by disorders of monoamine synthesis. In childhood and juvenile-onset cases, common genotypes include PRKN, HTT, ATP13A2, ATP1A3, FBX07, PINK1 and PLA2G6 mutations. Moreover, Wilson's disease and mutations in the manganese transporter are potentially treatable conditions and should always be considered in the differential diagnosis in any patient with early-onset parkinsonism.

Background Phosphoglycerate kinase-1 deficiency is caused by X-linked recessive mutations in PGK-1 and associated with haemolytic anaemia, rhabdomyolysis, myopathy and nervous system involvement. Some cases have been rarely associated with juvenile Parkinsonism however the causal relationship between PGK1 deficiency and nigrostriatal dysfunction causing Parkinsonism has not been determined. Objective and methods To investigate the nigrostriatal system using 99mTc-TRODAT-1 SPECT binding and report the phenotype of three affected males with early onset levodopa responsive Parkinsonism harbouring the c.491 A > T/p.D164V pathogenic variant. Results All patients initially presented with infantile-onset encephalopathic and stroke-like episodes, haemolytic anaemia and epilepsy. Two patients had an early-onset and one juvenile-onset levodopa responsive Parkinsonism with motor fluctuations. 99mTc-TRODAT-1 SPECT showed severe bilateral reduced putaminal uptake in the three patients. None of the patients had structural lesions that could explain either pre- or postsynaptic dopaminergic dysfunction. Conclusion These cases provide strong evidence of a causal relationship between PGK1 deficiency and nigrostriatal pathology causing Parkinsonism. These findings have potential implications for our understanding of the pathophysiology of nigrostriatal degeneration in sporadic PD.

Tremor is a phenomenon observed in a broad spectrum of diseases with different pathophysiologies. While patients with tremor may not complain in the clinic of symptoms of imbalance, gait difficulties, or falls, laboratory research studies using quantitative analysis of gait and posture and neurophysiologic techniques have demonstrated impaired gait and balance across a variety of tremor etiologies. These findings have been supported by careful epidemiologic studies assessing symptoms of imbalance. Imaging and neurophysiologic studies have identified cerebellar networks as important mediators of tremor, and therefore a likely common site of dysfunction to explain the phenomenologic overlap between impaired postural and gait control with tremor. Further understanding of these mechanisms and networks is of crucial importance in the development of new treatments, particularly surgical or minimally invasive lesional therapies.

The proband (patient 1), a 25-year-old woman, was the product of normal pregnancy and delivery. Her parents were first cousins from Lebanon. She sat at 6 months and crawled at 12 months. At age 3, she was noted to have developmental delay, hypotonia, and ataxia. The following year, she had a febrile illness and suspected absence seizure. EEG showed 4–5 Hz spike and slow wave complexes and she was treated with sodium valproate. At age 6, seizure frequency increased but improved with the addition of ethosuximide. Brain MRI at age 10 revealed increased T2 signal in both thalami and upper brainstem (figure). Serum and urinary amino acids, white blood cell lysosomal enzymes, serum lactate and pyruvate, liver function, and ammonia were normal. CSF neurotransmitters, glucose, and lactate were normal, although GABA was not measured. Her condition then remained static with occasional absence seizures. At age 22, she developed paroxysmal episodes of chorea in the neck, arms, and trunk associated with drowsiness, triggered by fever or hot weather (video 1). These occurred 4–5 times a year, lasting from 1 to 10 minutes. In all episodes, she remained responsive to verbal stimuli. Prolonged interictal video EEGs showed intermittent 4–6 Hz generalized epileptiform discharges, although no motor events were recorded.

Parkinson's disease justifies the use of deep brain stimulation (DBS) in certain patients who suffer from this condition. We present mid-term and long-term post-surgical outcomes in a cohort of 60 patients, who underwent DBS in the Hospital de Especialidades at Centro Médico Nacional Siglo XXI, in Mexico City.Patients underwent conventional stereotactic surgery with FrameLink software (Medtronics Inc). This technique consisted in the presurgical evaluation, the placement of stereotactic frame, imaging studies, preoperative planning procedure, microrecording, macrostimulation, as well as the placement of electrodes and generators in two phases. The variables were included in a data platform for Excel management. It was also included a variety of measurement instruments for data comparison. As a standard measure, it was used the Unified Parkinson Disease Rating Scale (UPDRS) before the surgery and at 3, 12, and 36 months.60 patients underwent surgery: 41 men and 19 women, with an average age of 56.5 years (39-70). There were good results in the majority of patients with preoperative UPDRS and at 3, 12 and 36 months of 79.57, 66.85, 65.29 and 58.75, respectively (p0.0001). There were complications in nine patients (15 %) and they were managed in a conservative manner.Postsurgical outcomes were from good to excellent in the majority of patients. Complications were minimal and conservatively managed. We propose the use of this procedure in a selected group of Parkinson's patients.Introducción: la enfermedad de Parkinson puede justificar un procedimiento quirúrgico que consiste en la estimulación cerebral profunda. Se presentan resultados a mediano y largo plazo de una cohorte de 60 pacientes del Hospital de Especialidades del Centro Médico Nacional Siglo XXI. Métodos: los pacientes fueron operados con una metodología estereotáctica convencional a través del protocolo FrameLink (Medtronics Inc.). La técnica consistió en la evaluación preoperatoria de los pacientes, la colocación de marco estereotáctico, la realización de estudios de imagen, la planeación preoperatoria, el microrregistro, la macroestimulación y la colocación de implantes, que estuvo conformada por electrodos y generador en dos fases. La escala unificada para la evaluación de la enfermedad de Parkinson (UPDRS) preoperatoria, a tres, 12, y 36 meses fue utilizada como medida estándar. Se analizaron los resultados y las complicaciones como variables de interés. Resultados: se operaron 60 pacientes (41 hombres y 19 mujeres), con edad promedio de 56.5 años (rango de 39-70). Se obtuvieron de buenos a excelentes resultados en la mayoría de los pacientes con UPDRS promedio en periodo preoperatorio, a 3, 12 y 36 meses de 79.57, 66.85, 65.29 y 58.75, respectivamente (p0.0001). Las complicaciones se presentaron en forma mínima (en nueve pacientes: 15 %) y fueron manejadas de forma conservadora. Conclusiones: hubo una mejoría progresiva en el UPDRS durante los 36 meses de seguimiento.

Objective To assess the frequency of postural and striatal deformities in patients with Parkinson’s disease. Patients and methods A total of 416 consecutive patients with Parkinson’s disease were evaluated for musculoskeletal deformities using a standardized criteria. Data including disease history, motor complications and antiparkinsonic treatment were collected. Results The overall frequency of musculoskeletal deformities was 19.7%. Striatal deformities were the most frequent deformities (9.9%). Scoliosis was the deformity most frequently found. No cases with Pisa syndrome or antecollis were found. Striatal deformities were associated with a younger age at onset, more frequent use of levodopa, as well as higher levodopa equivalent daily dose. Postural deformities were associated with higher motor scores. Conclusion Postural and striatal deformities are common in Parkinson’s disease. Striatal deformities appear to be more related to dopaminergic treatment, while postural deformities are associated with the motor state.

The Mexican Registry of Parkinson´s disease (ReMePARK) is nested within a multicentric cohort aimed to describe motor, non-motor, and genetic determinants of Parkinson's disease in Mexican patients.To date, clinical and demographic data from 1,083 subjects has been obtained. Here we present the demographic and clinical data of the current sample along with its comparison with international reports.A total of 607 male and 476 female subjects with Parkinson's disease were included. The mean age of the patients was 64.7 ± 12.9 years. The time from onset of symptoms to diagnosis was 2.4 ± 2.6 years. About 34% of subjects had only elementary education. Of the subjects, 54.4% were under treatment with dopamine agonists.Subjects with Parkinson's disease incorporated into ReMePARK are comparable with other international registries, with the exception of the years of formal education, time to diagnosis, and the use of dopamine agonists. The characterization of the Mexican population with Parkinson's disease will improve diagnosis and therapeutic management as well as define research efforts in this area. Finally, registry future directions are presented.

Gait abnormalities are prominent in atypical parkinsonian disorders and clinical signs such abnormal tandem walk have been suggested as a red flag for differential diagnosis. The objective is to determine the sensibility and specificity of the ten-steps test to discriminate atypical parkinsonisms from Parkinson's disease.A sample of subjects with a parkinsonian disorder was evaluated. The ten-steps test was applied to all subjects. A Bayesian analysis model was used to calculate sensibility and specificity.A total of 32 subjects with atypical parkinsonism and 54 subjects with Parkinson's disease were included. Abnormal tandem gait had a sensitivity of 90.6% and specificity of 66.6% to differentiate between groups. When adjusted to the actual atypical parkinsonism prevalence the positive predictive value fall from 61.7% to 13.8%.The ten-steps test provides additional information for the differential diagnosis in parkinsonian disorders but can only be regarded as a red flag.

Objective The aim of this study is to determine the usefulness of the University of Pennsylvania smell identification test (UPSIT), sniffin sticks (SS-16) and brief smell identification test (B-SIT) to assess smell identification in the Mexican population and its accuracy in discriminating subjects with Parkinson's disease (PD). Methods We included 199 nondemented PD subjects and 199 control subjects matched by gender. Smell identification was tested using the UPSIT and SS-16. Our group obtained B-SIT data from a previous report. Results The mean number of UPSIT items correctly identified by controls was 27.3±6; the PD group had a mean score of 19.4±6. UPSIT had a sensitivity of 82% with a specificity of 66% for a cut-off score of ≤25 for detection of PD. The mean number of SS-16 items correctly identified by controls was 10.3±2.2, while the PD group had 7.4±2.8 correct answers. For SS-16, sensitivity was 77.8% and specificity of 71.2% when using a cut-off value of ≤9. Lemon, turpentine and rose had an identification rate below the 25th percentile for all three tests. Odors with an identification rate above the 75th percentile include banana for all three tests, and gasoline, onion and chocolate for UPSIT and B-SIT. Conclusion The sensitivity and specificity of the smell tests that were evaluated were lower in comparison to other published reports. Cultural biases and smell familiarity may influence the test results. The development of a true cross-culturally adapted smell identification test is warranted may improve test accuracy.

Underweight and malnutrition are well documented in Parkinson's disease (PD), while overweight has been less reported. We carried out a cross-sectional study including 177 healthy controls and 177 PD patients attending a tertiary care center. We recorded weight and height for all participants. A statistically significant difference was found in body mass index (BMI) between controls and PD patients (29.1±5.4 versus 27.2±4.7, p

Parkinson's disease (PD) is the second most common chronic neurodegenerative disorder. PD is clinically characterized by a constellation of motor and nonmotor symptoms that may have a direct effect on daily activities as well as in the quality of life of the patient. Identifying the symptoms more closely associated with a poor quality of life is central on improving the medical care of the patient. We undertook this study to identify and describe the clinical and demographic factors that predict health-related quality of life among Mexican patients with PD.One hundred seventy-seven patients with Parkinson's disease were included. Patients were evaluated using the following clinimetric instruments: motor subscale of the Unified Parkinson's disease rating scale, Hoehn and Yahr stage, Non-motor Symptoms Questionnaire, Parkinson's disease Questionnaire (PDQ-39) and the Mini Mental Status Examination.Multivariate analysis showed that the main factors associated with a poor quality of life were motor impairment (β = 0.27, p0.001) and the number of nonmotor symptoms (β = 2.17, p0.001). The main nonmotor domains impacting on the quality of life were depression/anxiety (β = 6.36, p0.001), cardiovascular (β = 5.39, p = 0.001), memory (β = 4.64, p0.001) and miscellaneous (β = 3.15, p = 0.001).Both motor and mainly nonmotor symptoms are negatively associated with health-related quality of life in patients with PD and should be appropriately attended in order to improve patient care.

Opsoclonus myoclonus syndrome (OMS) is a rare disorder characterized by involuntary, multidirectional, chaotic saccades; head, limb, and trunk action myoclonus; and other associated features including cerebellar ataxia, encephalopathy, postural tremor, and sleep and behavioral disruption. 1 OMS can occur as a paraneoplastic or nonparaneoplastic syndrome. In both cases, an autoimmune pathophysiology has been proposed. 1,2 We report a 37-year-old man who developed an upper respiratory tract infection. Five days later, he developed paroxysms of blurred vision and oscillopsia. He had prominent neck myoclonus that ceased when supine but was provoked by sitting up, standing, or walking. Truncal instability was present, resulting in an inability to walk unassisted. Neurological examination (see Video) revealed eye movements with periodic, rapid, conjugated chaotic ocular oscillations that were independent of eye position and occurred during fixation, regardless of gaze direction, with eyes open or closed. Disabling ataxia of the trunk, limbs, and gait was present with stimulus-sensitive myoclonus. Cerebrospinal fluid (CSF) analysis showed lymphocytic pleocytosis and unmatched oligoclonal bands. Full blood count, serum chemistry, thyroid profile, cardiolipin, lupus anticoagulant, and dsDNA antibodies, Yo, Hu, Ri antibodies, brain CT and MRI, and

Objectives. This study prospectively evaluated whether transdermal nitroglycerin patches could limit the extent of exercise-induced left ventricular ischemia as assessed by quantitative thallium-201 tomography. Background. Although antianginal medications are effective at reducing chest pain symptoms in patients with coronary artery disease, there is limited evidence that these agents can also reduce myocardial ischemia. Methods. This was a randomized, double-blind, parallel, placebo-controlled trial evaluating nitroglycerin patch therapy in patients in stable condition with angiographic coronary artery disease and no previous myocardial infarction. All patients were weaned from antianginal agents and had a baseline symptom-limited treadmill test followed by thallium-201 tomography. Forty patients with perfusion defects involving ≥5% of the left ventricle were randomized to receive either intermittent (12 h on/off) active nitroglycerin patch therapy (0.4 mg/h) or placebo. Exercise tomography was repeated a mean (±SD) of 6.1 ± 1.8 days after randomization. Results. Patients randomized to receive active patch therapy had a significant reduction in their total perfusion defect size (−8.9 ± 11.1%) compared with placebo-treated patients (−1.8 ± 6.1%, p = 0.04), which was most apparent in those with the largest (≥20%) baseline perfusion defects (−11.4 ± 13.4% vs. 1.0 ± 3.6%, respectively, p < 0.02). Furthermore, 7 (33%) of 21 patients receiving active therapy had a ≥10% decrease in their perfusion defects compared with only 1 (5%) of 19 patients randomiztd to receive placebo (p = 0.002). Nitrate therapy did not significantly reduce heart rate, blood pressure or double product, indicating benefit through enhancement of coronary blood flow. Conclusions. Short-term, intermittent nitroglycerin patch therapy significantly reduces myocardial ischemia, particularly in patients with large ischemic perfusion defects. Thallium-201 tomography can be used to assess sequential changes in the extent of exercise-induced left ventricular ischemia.

Parkinson's disease is a neurodegenerative disorder characterized by bradykinesia, resting tremor and rigidity. Pathologically, Parkinson's disease is defined by the presence of Lewy bodies, which result from the aggregation of alpha-synuclein. Braak, et al. have proposed that the aggregation of alpha-synuclein pathology in Parkinson's disease begins in the medulla oblongata and progresses predictably, reaching the substantia nigra in the midbrain after affecting the brain stem. Apart from the motor symptoms of the disease, non-motor symptoms may precede the evoked potentials, and these include cognitive dysfunction, psychiatric disorder, sleep disorders and autonomic dysfunction.To describe and discuss the non-motor symptoms and diagnostic tests and procedures which may provide a pre-motor diagnosis of Parkinson's disease.Non-motor symptoms are now accepted as an integral part of the clinical spectrum of Parkinson's disease and there is evidence to suggest that olfactory dysfunction and sleep disturbances may occur before motor signs. The presence of various non-motor symptoms in conjunction with imaging studies has the potential to detect patients with Parkinson's disease in the pre-motor phase. Nevertheless, a larger number of studies are required, in particular cohort design of subjects in risk.

This study sought to evaluate the efficacy and safety of fasudil, an orally available rho kinase inhibitor, in patients with stable angina.Several small, non-placebo-controlled trials suggest that fasudil reduces myocardial ischemia in patients with stable or vasospastic angina.In a multicenter, double-blind, placebo-controlled, randomized trial, the efficacy and safety of fasudil were evaluated in stable angina patients. Of the 206 patients screened, 84 patients with reproducible exercise times were randomized 1:1 to fasudil or placebo. Nitroglycerin as needed and a beta- or calcium-channel blocker were allowed. Fasudil or matching placebo was force-titrated from 20 mg three times daily to 80 mg twice daily with 20 mg twice-daily increments every two weeks. Symptom-limited exercise testing was performed after two, four, six, and eight weeks of treatment.At peak, exercise duration was significantly improved at all visits in both groups, although exercise duration was numerically greater in patients receiving fasudil versus those receiving placebo. Time toor =1 mm ST-segment depression was increased with fasudil at both peak and trough compared with placebo (172.1 s vs. 44.0 s, p = 0.001, and 92.8 s vs. 26.4 s, p = 0.02, respectively). Fasudil improved Seattle Angina Questionnaire scores. No significant differences in Canadian Cardiovascular Society class, time to angina, or frequency of angina or nitroglycerin use were noted between groups. Fasudil did not affect heart rate or blood pressure, and was well tolerated.Fasudil up to 80 mg three times daily significantly increased the ischemic threshold of angina patients during exercise with a trend toward increased exercise duration. Further investigation of fasudil doses80 mg three times daily is indicated.

A study of septal Q wave response in lead CM5 was carried out to evaluate its usefulness in predicting coronary artery disease. Q wave amplitude was measured in 50 patients with coronary artery disease and 50 normal subjects before and immediately after exercise. In the 100 patients evaluated with coronary angiography, the septal Q wave in lead, CM5 was smaller in patients with coronary artery disease than in normal subjects at rest (probability [p] less than 0.001) and immediately after exercise (p less than 0.001). An embryonic (0.5 mm) or absent Q wave in lead CM5 was significantly more frequent in patients with coronary artery disease than in normal subjects both at rest (76 versus 48 percent) and after exercise (82 versus 16 percent). The sensitivity for S-T depression was 52 percent, the specificity 74 percent and the predictive value 70 percent. The respective values for Q wave were 82, 88 and 87 percent. These differences were not significant (p less than 0.05). When either a positive S-T or Q wave response was used, the sensitivity increased to 92 percent (p less than 0.05), and the specificity and predictive values remained unchanged (p less than 0.01). An increase in Q wave amplitude with exercise identified a false positive S-T segment response to stress in 75 percent of cases. Absence of the Q wave in lead CM5 with S-T depression after identified a true positive response in 100 percent of cases. These findings suggest that low Q wave voltage and it failure to increase after exercise imply abnormal septal activation, reflecting loss of contraction associated with ischemia. This finding may be a useful marker for ischemia; the increase in the septal Q wave with exercise may be of value in identifying a false positive S-T segment response.

© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited., Background: As gene-targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial-ready cohorts is limited. Objective: The objectives are to (1) establish an international cohort of affected and unaffected individuals with PD-linked variants; (2) provide harmonized and quality-controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD. Methods: We conducted a worldwide, systematic online survey to collect individual-level data on individuals with PD-linked variants in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ-1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype-phenotype relationships were analyzed. Results: We collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ-1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published. Conclusions: Within the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD-linked variants; (2) provide harmonized and quality-controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene-targeted clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., Michael J. Fox Foundation for Parkinson's Research. Grant Number: ID 15015.02. NIHR Cambridge Biomedical Research Centre. Grant Number: BRC-1215-20014