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Background There is currently no undisputed, validated, clinically meaningful measure for deficits in the broad spectrum of PSP phenotypes. Objective To develop a scale to monitor clinical deficits in patients with PSP across its broad phenotypes. Methods The Progressive Supranuclear Palsy Clinical Deficits Scale was conceptualized to cover seven clinical domains (Akinesia‐rigidity, Bradyphrenia, Communication, Dysphagia, Eye movements, Finger dexterity, and Gait & balance), each scored from 0 to 3 (no, mild, moderate, or severe deficits). User guidelines were developed to standardize its application. Progressive Supranuclear Palsy Clinical Deficits Scale scores were collected in patients fulfilling the MDS‐PSP diagnostic criteria in two independent, multicenter, observational studies, both cross‐sectionally (exploratory DescribePSP cohort; confirmatory ProPSP cohort) and longitudinally (12‐months’ follow‐up, both cohorts). Results Cognitive pretesting demonstrated easy scale utility. In total, 164 patients were scored (70.4 ± 7.6 years; 62% males, 35% variant phenotypes). Mean Progressive Supranuclear Palsy Clinical Deficits Scale completion time was 4 minutes. The Progressive Supranuclear Palsy Clinical Deficits Scale total score correlated with existing scales (e.g., Progressive Supranuclear Palsy Rating Scale: R = 0.88; P < 0.001). Individual Progressive Supranuclear Palsy Clinical Deficits Scale items correlated well with similar constructs in existing scales. Internal consistency (Cronbach's alpha: 0.75), inter‐rater reliability (0.96), and test‐retest stability (0.99) were acceptable. The PSP‐CDS showed significant 12‐month change (baseline, 8.6 ± 3.6; follow‐up: 10.8 ± 3.6; annualized difference: 3.4 ± 3.4; n = 49; P < 0.0001). Sample sizes required per arm for a two‐arm, 1‐year follow‐up therapeutic trial to detect 50% change in Progressive Supranuclear Palsy Clinical Deficits Scale progression was estimated to be 65 (two‐sided, two‐sample t test). Conclusion The Progressive Supranuclear Palsy Clinical Deficits Scale is a rapidly completed, clinimetrically sound scale for clinical care and research involving PSP. © 2020 International Parkinson and Movement Disorder Society

Neuroblasts born in the subventricular zone of adult mammals migrate via the rostral migratory stream into the granular cell layer or periglomerular layer of the olfactory bulb to differentiate into interneurons. To analyze if new neurons in the granular cell layer or periglomerular layer have different origins, we inserted a physical barrier into the rostral migratory stream, depleted cell proliferation with cytarabine infusions, labeled newborn cells with bromodeoxyuridine, and sacrificed mice after short-term (0, 2, or 14 days) or long-term (55 or 105 days) intervals. After short-term survival, the subventricular zone and rostral migratory stream rapidly repopulated with bromodeoxyuridine+ cells after cytarabine-induced depletion. Nestin, glial fibrillary acidic protein and the PAX6 were expressed in bromodeoxyuridine+ cells within the rostral migratory stream downstream of the physical barrier. After long-term survival after physical barrier implantation, bromodeoxyuridine+ neurons were significantly reduced in the granular cell layer, but bromodeoxyuridine+ and dopaminergic neurons in the periglomerular layer remained unaffected by the physical barrier. Thus, newborn neurons for the granular cell layer are mainly recruited from neural stem cells located in the subventricular zone, but new neurons for the periglomerular layer with dopaminergic predisposition can rise as well from neuronal stem or precursor cells in the rostral migratory stream.

Pearls cOcular motor apraxia (OA) is an inability to initiate voluntary saccades in a head-fixed position, while saccades can be initiated by the vestibulo-ocular reflex (indicating dysfunction in the frontal eye fields). We report a case exemplifying the clinical differentiation between OA and SGP and discuss their relevance for topical diagnosis in neurology.Case report A right-handed 49-year-old man was referred to us for diagnostic evaluation with suspected progressive supranuclear palsy (PSP) with predominant parkinsonism 1,2 when he developed impairments of vertical and horizontal eye movement control after a 2-year history of progressive slowing of the left limbs and jerky movements of the left hand. He had no family history of neuropsychiatric diseases. Eighteen months after symptom onset, cerebral MRI had suggested mild right-sided parietal cortical atrophy and normal midbrain size, [123 I]-FP-CIT SPECT had revealed right-sided loss of presynaptic striatal dopamine transporter-positive nerve terminals, and [ 123 I]-iodobenzamide SPECT had shown bilateral symmetric reduction of the postsynaptic striatal D2 receptor expressing neurons. A therapeutic trial with 800 mg of levodopa per day had not yielded symptomatic benefit.Upon admission, the patient was independent in his activities of daily living. He and his wife perceived his cognition, language, speech, and personality as unimpaired. Comprehensive neuropsychological testing was normal. Physical examination showed mild bradykinesia and rigidity with cogwheeling in the left but not in the right limbs (video 1, links.lww.com/WNL/ A220). The left arm showed mild stimulus-sensitive myoclonus. Resting, postural, or action tremor were not observed. Gait examination showed reduced left-sided arm swing. Postural stability was normal. Limb or orobuccal apraxia, alien limb phenomena, and cortical sensory MORE ONLINE Video links.lww.com/WNL/A220

Olanzapine is a second-generation antipsychotic drug which is generally considered safe with well therapeutic antipsychotic effects. We describe a patient suffering from bilateral intracerebral hemorrhage after severe olanzapine intoxication without underlying thrombocytopenia, arterial hypertension, or vascular malformation as cause of intracerebral hemorrhage. This raises the possibility of a direct side effect of high-dose olanzapine intake. So far, intracranial hemorrhage after olanzapine intoxication in such constellation has not been reported before. Given the high number of its prescription rates, our finding of intracranial hemorrhage after olanzapine intoxication is of high clinical relevance.

Atypical Parkinson syndromes are a heterogeneous group of neurodegenerative diseases which present with parkinsonism and other non-motor symptoms. On the basis of the underlying pathology, namely the abnormal aggregation of the proteins alpha-synuclein or tau, atypical Parkinson syndromes can be divided into synucleinopathies (multiple system atrophy, Lewy body dementia) and tauopathies (progressive supranuclear palsy, corticobasal degeneration). Currently there are no effective treatments to slow down disease progression available. Medications which help to manage the symptoms show only temporary and insufficient efficacy. In recent years, preclinical research identified essential steps in the pathogenesis of the diseases. Treatments which inhibit pathological protein aggregation and its spreading were developed and showed promising results in animal models. First clinical trials of causal treatments targeting the underlying pathomechanism have been finished; several trials are recruiting patients or being planned at the moment. In the following article we present the latest developments regarding the causal therapy of atypical Parkinson syndromes and the current clinical trials.

The field of tauopathies is in a state of dynamic and rapid progress, requiring close interdisciplinary collaboration.

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