Emergency presentations of movement disorders.

Movement disorders are typically perceived as being gradually progressive conditions that are managed in outpatient settings. However, they may manifest de novo with an acute severe phenotype or an acute decompensation. A movement disorder becomes an emergency when it evolves acutely or subacutely over hours to days; delays in its diagnosis and treatment may cause significant morbidity and mortality. Here we address the clinical presentation, diagnosis and management of those movement disorder emergencies that are principally encountered in emergency departments, in acute receiving units or in intensive care units. We provide practical guidance for management in the acute setting where there are several treatable causes not to be missed. The suggested medication doses are predominantly based on expert opinion due to limited higher-level evidence. In spite of the rarity of movement disorder emergencies, neurologists need to be familiar with the phenomenology, potential causes and treatments of these conditions. Movement disorder emergencies divide broadly into two groups: hypokinetic and hyperkinetic, categorised according to their phenomenology. Most acute presentations are hyperkinetic and some are mixed.

Elevated urine BMP phospholipids in LRRK2 and VPS35 mutation carriers with and without Parkinson's disease.

Elevated urine bis(monoacylglycerol)phosphate (BMP) levels have been found in gain-of-kinase function LRRK2 G2019S mutation carriers. Here, we have expanded urine BMP analysis to other Parkinson's disease (PD) associated mutations and found them to be consistently elevated in carriers of LRRK2 G2019S and R1441G/C as well as VPS35 D620N mutations. Urine BMP levels are promising biomarkers for patient stratification and potentially target engagement in clinical trials of emerging targeted PD therapies.

Parkinson's disease is overdiagnosed clinically at baseline in diagnostically uncertain cases: a 3-year European multicenter study with repeat [123I]FP-CIT SPECT.

Overdiagnosis of Parkinson's disease (PD) is suggested by specialist review of community diagnosis, and in postmortem studies. In specialist centers 4 to 15% of patients entered into clinical trials as early PD do not have functional imaging support for a PD diagnosis. In a European multicenter, prospective, longitudinal study, we compared clinical diagnosis with functional SPECT imaging using [123I]FP-CIT (DaTSCAN, GE Healthcare). Repeat observations were performed over 3 years in patients with tremor and/or parkinsonism in whom there was initial diagnostic uncertainty between degenerative parkinsonism and nondegenerative tremor disorders. Video-recording of clinical features was scored independently of functional imaging results by two blinded clinicians at 36 months (= gold standard clinical diagnosis). Three readers, unaware of the clinical diagnosis, classified the images as normal or abnormal by visual inspection. The main endpoint was the sensitivity and specificity of SPECT imaging at baseline compared with the gold standard. In 99 patients completing the three serial assessments, on-site clinical diagnosis overdiagnosed degenerative parkinsonism at baseline in diagnostically uncertain cases compared with the gold standard clinical diagnosis (at 36 months), the latter giving a sensitivity of 93% and specificity of 46%. The corresponding baseline [123I]FP-CIT SPECT results showed a mean sensitivity of 78% and a specificity of 97%. Inter-reader agreement for rating scans as normal or abnormal was high (Cohen's kappa = 0.94-0.97).

Two-year follow-up in 150 consecutive cases with normal dopamine transporter imaging.

BACKGROUND AND AIMS: Functional pre-synaptic dopamine brain imaging is generally abnormal when parkinsonism is degenerative (such as in idiopathic Parkinson's disease) and normal in patients with non-degenerative movement disorder (such as essential tremor). However, some patients diagnosed as early Parkinson's disease have normal presynaptic dopamine imaging. Follow-up of patients with normal imaging should help determine whether such patients truly have degenerative parkinsonism (and therefore represent false negative imaging results), or emerge as cases of non-degenerative parkinsonism (and therefore represent initial clinical over-diagnosis of Parkinson's disease). METHODS AND RESULTS: One hundred and fifty cases with normal I-FP-CIT SPECT undertaken during routine care over a 3-year period were reviewed 2.4 years (interquartile range, 2.2-3.1 years) after SPECT. Diagnosis after follow-up was non-degenerative parkinsonism or tremor in 146 (97%), who did not progress clinically, and degenerative parkinsonism in four (3%), in whom clinical progression was noted. Anti-Parkinson therapy was used in 36, and withdrawn in 27 with no deterioration in 25. Patients strictly fulfilling Brain Bank criteria (part 1) were more likely to undergo a trial of anti-Parkinson therapy (P < 0.05) but were no more likely to maintain or respond to anti-Parkinson therapy than those not fulfilling criteria. CONCLUSION: The clinical profile and therapy response during follow-up of patients with normal presynaptic dopamine imaging supports the diagnosis of a non-degenerative movement disorder in nearly all cases.

Successful antiparkinsonian medication withdrawal in patients with Parkinsonism and normal FP-CIT SPECT.

Between 4% and 14% of patients diagnosed with Parkinson's disease and entering clinical trials have normal presynaptic dopaminergic imaging. The effects of antiparkinsonian therapy have varied in these studies, and the consequences of stopping treatment are not reported. We present 11 patients who initially fulfilled diagnostic criteria and were treated for Parkinson's disease but in whom emerging diagnostic doubts led to antiparkinsonian therapy withdrawal, which was achieved without deterioration. Such cases represent a nondegenerative form of Parkinsonism, which does not benefit from dopaminergic therapy. Prospective vigilance regarding this category is of importance in clinical practice and clinical trials.