An MRI time course of 512 echo-planar images (EPI) in resting human brain obtained every 250 ms reveals fluctuations in signal intensity in each pixel that have a physiologic origin. Regions of the sensorimotor cortex that were activated secondary to hand movement were identified using functional MRI methodology (FMRI). Time courses of low frequency (< 0.1 Hz) fluctuations in resting brain were observed to have a high degree of temporal correlation (P < 10(-3)) within these regions and also with time courses in several other regions that can be associated with motor function. It is concluded that correlation of low frequency fluctuations, which may arise from fluctuations in blood oxygenation or flow, is a manifestation of functional connectivity of the brain.

Functional connectivity in the motor cortex of resting human brain using echo-planar MRI.

Objective: Parkinson’s disease (PD) is a progressive neurological disorder characterised by a large number of motor and non-motor features that can impact on function to a variable degree. This review describes the clinical characteristics of PD with emphasis on those features that differentiate the disease from other parkinsonian disorders. Methods: A MedLine search was performed to identify studies that assess the clinical characteristics of PD. Search terms included “Parkinson’s disease”, “diagnosis” and “signs and symptoms”. Results: Because there is no definitive test for the diagnosis of PD, the disease must be diagnosed based on clinical criteria. Rest tremor, bradykinesia, rigidity and loss of postural reflexes are generally considered the cardinal signs of PD. The presence and specific presentation of these features are used to differentiate PD from related parkinsonian disorders. Other clinical features include secondary motor symptoms (eg, hypomimia, dysarthria, dysphagia, sialorrhoea, micrographia, shuffling gait, festination, freezing, dystonia, glabellar reflexes), non-motor symptoms (eg, autonomic dysfunction, cognitive/neurobehavioral abnormalities, sleep disorders and sensory abnormalities such as anosmia, paresthesias and pain). Absence of rest tremor, early occurrence of gait difficulty, postural instability, dementia, hallucinations, and the presence of dysautonomia, ophthalmoparesis, ataxia and other atypical features, coupled with poor or no response to levodopa, suggest diagnoses other than PD. Conclusions: A thorough understanding of the broad spectrum of clinical manifestations of PD is essential to the proper diagnosis of the disease. Genetic mutations or variants, neuroimaging abnormalities and other tests are potential biomarkers that may improve diagnosis and allow the identification of persons at risk.

https://jnnp.bmj.com/content/jnnp/79/4/368.full.pdf

Parkinson’s disease: clinical features and diagnosis

This document presents the Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's disease (PD). The Movement Disorder Society PD Criteria are intended for use in clinical research but also may be used to guide clinical diagnosis. The benchmark for these criteria is expert clinical diagnosis; the criteria aim to systematize the diagnostic process, to make it reproducible across centers and applicable by clinicians with less expertise in PD diagnosis. Although motor abnormalities remain central, increasing recognition has been given to nonmotor manifestations; these are incorporated into both the current criteria and particularly into separate criteria for prodromal PD. Similar to previous criteria, the Movement Disorder Society PD Criteria retain motor parkinsonism as the core feature of the disease, defined as bradykinesia plus rest tremor or rigidity. Explicit instructions for defining these cardinal features are included. After documentation of parkinsonism, determination of PD as the cause of parkinsonism relies on three categories of diagnostic features: absolute exclusion criteria (which rule out PD), red flags (which must be counterbalanced by additional supportive criteria to allow diagnosis of PD), and supportive criteria (positive features that increase confidence of the PD diagnosis). Two levels of certainty are delineated: clinically established PD (maximizing specificity at the expense of reduced sensitivity) and probable PD (which balances sensitivity and specificity). The Movement Disorder Society criteria retain elements proven valuable in previous criteria and omit aspects that are no longer justified, thereby encapsulating diagnosis according to current knowledge. As understanding of PD expands, the Movement Disorder Society criteria will need continuous revision to accommodate these advances.

/pdf/mds-clinical-diagnostic-criteria-for-parkinson-s-disease-74dzuucoq6.pdf

MDS clinical diagnostic criteria for Parkinson's disease

Measuring Health: A Guide to Rating Scales and Questionnaires

BACKGROUND: Neurostimulation of the subthalamic nucleus reduces levodopa-related motor complications in advanced Parkinson's disease. We compared this treatment plus medication with medical management. METHODS: In this randomized-pairs trial, we enrolled 156 patients with advanced Parkinson's disease and severe motor symptoms. The primary end points were the changes from baseline to six months in the quality of life, as assessed by the Parkinson's Disease Questionnaire (PDQ-39), and the severity of symptoms without medication, according to the Unified Parkinson's Disease Rating Scale, part III (UPDRS-III). RESULTS: Pairwise comparisons showed that neurostimulation, as compared with medication alone, caused greater improvements from baseline to six months in the PDQ-39 (50 of 78 pairs, P=0.02) and the UPDRS-III (55 of 78, P<0.001), with mean improvements of 9.5 and 19.6 points, respectively. Neurostimulation resulted in improvements of 24 to 38 percent in the PDQ-39 subscales for mobility, activities of daily living, emotional well-being, stigma, and bodily discomfort. Serious adverse events were more common with neurostimulation than with medication alone (13 percent vs. 4 percent, P<0.04) and included a fatal intracerebral hemorrhage. The overall frequency of adverse events was higher in the medication group (64 percent vs. 50 percent, P=0.08). CONCLUSIONS: In this six-month study of patients under 75 years of age with severe motor complications of Parkinson's disease, neurostimulation of the subthalamic nucleus was more effective than medical management alone. (ClinicalTrials.gov number, NCT00196911 [ClinicalTrials.gov].).

/pdf/a-randomized-trial-of-deep-brain-stimulation-for-parkinson-s-40jf18b006.pdf

A Randomized Trial of Deep-Brain Stimulation for Parkinson's Disease

Paroxysmal non-kinesigenic dyskinesia (PNKD) is a rare disorder which typically begins in childhood. Attacks are characterized by a combination of dystonia and chorea, and they are usually triggered by alcohol, coffee, or strong emotion. Attacks can last from 5 min to 4 h. MR-1, which is now called PNKD gene, is the disease-causing gene in “primary” PNKD. Clonazepam appears to be the most successful treatment for PNKD. Deep brain stimulation of internal part of globus pallidus can be a treatment option in medication-resistant cases.

Paroxysmal Non-kinesigenic Dyskinesia

Objective: Botulinum toxin is widely utilized as a first-line therapy for cervical dystonia (CD). Numerous studies have demonstrated the efficacy and safety of this treatment, but little data exist on patient satisfaction. To address this question, a structured patient survey was conducted in Germany, France, the US, and Canada (n ¼ 136 patients with CD).

https://informahealthcare.com/doi/pdf/10.3111/13696998.2011.653726

Original article Satisfaction with botulinum toxin treatment: a cross-sectional survey of patients with cervical dystonia

Therapeutics of Paroxysmal Dyskinesias

Although MR-1/PNKD variants are the most common cause of inherited paroxysmal non-kinesigenic dyskinesia (PNKD), in a large proportion of PNKD patients, the underlying genetic basis remains unknown. Pyruvate dehydrogenase (PDH) complex deficiency causes phenotypes ranging from fatal infantile lactic acidosis to mental retardation or intermittent ataxia. Brain imaging may reveal cortical atrophy, ventricular dilatation, basal ganglia (BG) abnormalities, and corpus callosum agenesis. PDH deficiency might result from variants in genes encoding discrete subunits of the PDH complex. The majority is caused by PDHA1 variants, whereas a minority is caused by variants in PDHB, DLAT, DLD, PDHX, or PDP1. Paroxysmal dyskinesia (PxD) is an infrequent, poorly characterized feature in a few cases of PDH deficiency caused by PDHA1 or DLAT variants. Here, we report isolated PNKD in 2 siblings, associated with a novel homozygous pathogenic variant in PDHB, the gene coding for the E1β subunit of the PDH complex. The siblings were born to consanguineous parents of Indian origin (Fig. 1A). The proband (II-1) experienced repeated falls due to episodes of hemior bilateral lower-limb predominant dystonia, with onset at age 5 years (Video S1, Segment 1). The episodes typically lasted 1 to 2 hours, were not precipitated by movement, and would occur without warning. Interictal examination was normal. Serum biochemistry, electrolytes, calcium, urine gas chromatography/tandem mass spectrometry for metabolic diseases, and tests for Wilson’s disease were unrevealing. Nerve conduction studies and electroencephalograms were normal. Lactate and pyruvate levels in blood and cerebrospinal fluid were normal, as observed previously in individuals with DLAT variants. Brain magnetic resonance imaging (MRI) revealed symmetric T2 pallidal hyperintensities on T2 and FLAIR (Fig. 1C, II-1). Levodopa, trihexyphenidyl, clonazepam, and baclofen were unhelpful. Carbamazepine (CBZ) at 300 mg/day led to a 90% to 95% reduction in frequency, severity, and duration of the episodes. Three years later, his younger brother (II-2) manifested identical episodic hemidystonia mainly affecting one foot or leg (Video S2, Segment 2), with T2 hyperintensities in the dentate nucleus (Fig. 1C, II-2). His attacks also responded nearcompletely to CBZ (200 mg/day). Pallidal lesions in patients with isolated paroxysmal dystonia have been described in patients with PDH deficiency (due to variants in DLAT, PDHA1, and PDHX) and due to ECHS1 variants. However, analysis in the proband’s WES (Whole Exome Seqencing) (Appendix S1) did not reveal any variants in these genes or other genes causing PxD (Table S1). Instead, we found a homozygous variant in PDHB, c.856A>G/p.Thr286Ala (Table S2), absent in databases and predicted damaging by most in silico tools (Table S3). The phenotypic spectrum observed with biallelic PDHB variants is similar to that observed with PDHA1 but with unclear genotype–phenotype correlations. A review of 82 patients with PDH deficiency included 65 patients with PDHA1 variants, 9 with PDHX, 7 with PDHB, and 1 with DLD. In these patients, dystonia was reported in those with PDHA1 and PDHX variants but in none with PDHB variants. In contrast, mild dystonia without additional clinical characterization was mentioned in 1 patient with PDHB variants and other clinical features. Furthermore, other PDHB patients showed abnormal BG/dentate MRI lesions. To our knowledge, isolated paroxysmal dystonia has not been described in patients with PDHB variants. After the identification of the PDHB variant, the siblings were commenced on thiamine and multivitamin supplementation. The younger brother continues to respond to CBZ, without attack recurrence. In contrast, the proband remains asymptomatic at 3-year follow-up after stopping CBZ. These observations might be of therapeutic relevance, given reports of improvement and even complete reversibility in some patients after thiamine. A trial of thiamine supplementation should be considered in cases of isolated PNKD or PED (Paroxysmal Exercise-induced dyskinesia) with bilateral pallidal lesions. In conclusion, our patients with PNKD as the only and prominent clinical presentation represent a relevant expansion of the phenotype associated with PDHB. Our observation suggests that PDHB should be included among the genetic causes of isolated PNKD.

/pdf/isolated-paroxysmal-non-kinesigenic-dystonia-associated-with-2km9q9so.pdf

Isolated Paroxysmal Non‐kinesigenic Dystonia Associated with Homozygous PDHB Variant in an Indian Family

In the growth of technology there have been some discussions recently regarding the use of such technology and how they affect hotels function as technology has advanced, the hotel sector has begun using state-of-the-art technologies such as Machine Learning (ML) and robots. Several recent discussions have been held on the use of these technologies and how they affect the cost of running hotels. With these new technologies becoming increasingly important, this paper examines the trend of the hotel industry’s adoption of machine learning and robotics. To determine the fundamental elements that influence ML adoption, we used the TOE framework across three domains: technology, organization, and environment. The finding expose the hotels are using ML and robotics due to the numerous factors that influence their adoption. The study illustrates how machine learning could be implemented in the hospitality sector and is one of the initial efforts to explore the full scope of how it may be applied.

The Acceptance of Machine module in the Hospitality Industry with Prospects and Challenges: A Review

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