Alexander Pantelyat

Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria.

Background: PSP is a neuropathologically defined disease entity. Clinical diagnostic criteria, published in 1996 by the National Institute of Neurological Disorders and Stroke/Society for PSP, have excellent specificity, but their sensitivity is limited for variant PSP syndromes with presentations other than Richardsons syndrome.

Which ante mortem clinical features predict progressive supranuclear palsy pathology

Progressive supranuclear palsy (PSP) is a neuropathologically defined disease presenting with a broad spectrum of clinical phenotypes.

Radiological Biomarkers for Diagnosis in PSP: Where Are We and Where Do We Need to Be?

PSP is a pathologically defined neurodegenerative tauopathy with a variety of clinical presentations including typical Richardsons syndrome and other variant PSP syndromes. A large body of neuroimaging research has been conducted over the past two decades, with many studies proposing different structural MRI and molecular PET/SPECT biomarkers for PSP. These include measures of brainstem, cortical and striatal atrophy, diffusion weighted and diffusion tensor imaging abnormalities, [18F] fluorodeoxyglucose PET hypometabolism, reductions in striatal dopamine imaging and, most recently, PET imaging with ligands that bind to tau. Our aim was to critically evaluate the degree to which structural and molecular neuroimaging metrics fulfill criteria for diagnostic biomarkers of PSP. We queried the PubMed, Cochrane, Medline, and PSYCInfo databases for original research articles published in English over the past 20 years using postmortem diagnosis or the NINDS‐SPSP criteria as the diagnostic standard from 1996 to 2016. We define a five‐level theoretical construct for the utility of neuroimaging biomarkers in PSP, with level 1 representing group‐level findings, level 2 representing biomarkers with demonstrable individual‐level diagnostic utility, level 3 representing biomarkers for early disease, level 4 representing surrogate biomarkers of PSP pathology, and level 5 representing definitive PSP biomarkers of PSP pathology. We discuss the degree to which each of the currently available biomarkers fit into this theoretical construct, consider the role of biomarkers in the diagnosis of Richardsons syndrome, variant PSP syndromes and autopsy confirmed PSP, and emphasize current shortfalls in the field.

Acalculia in Autopsy-Proven Corticobasal Degeneration

Corticobasal degeneration (CBD) is a neurodegenerative condition presenting with an asymmetric extrapyramidal disorder, cortical sensory loss, and apraxia. While the original case descriptions mentioned acalculia,1 few studies have investigated this,2,3 and reports of acalculia in autopsy-proven CBD are very rare. We detail 2 autopsy-defined CBD cases with acalculia to emphasize that CBD compromises cognitive functioning due to disease that includes parietal cortex. ### Case 1. A 72-year-old right-handed woman with hypertension and hypothyroidism was evaluated for progressive cognitive and motor difficulties over 3 years. She first noted writing difficulty. Her right hand began performing involuntary, semi-purposeful movements. She required increasing assistance dressing and cutting food. She misjudged spatial relationships while driving and cooking. She had several falls. Examination revealed Mini-Mental State Examination (MMSE) score of 27. She had ideomotor apraxia, slowed writing, and difficulty copying geometric designs. Number knowledge was impaired, including miscounting “X” marks on a paper and erring during oral and written calculations (e.g., given “9 + 12,” she responded “20”). Memory, digit span, reading, comprehension, and speech were intact. She had axial rigidity and decreased right arm swing, but no other involuntary movements. Neuropsychological evaluation ( z scores relative to 25 demographically matched controls) revealed deficits on spatial tasks (e.g., geometric figure copy z = −7.74), mild executive dysfunction (e.g., animal category naming fluency z = −1.90), and preserved language (e.g., Boston Naming test z = −0.86) and memory (delayed recall of a 10-word list z = 0.02). MRI showed parietal atrophy. Over the next 18 months, ideomotor apraxia worsened, and she …

C9orf72 Hexanucleotide Repeat Analysis in Cases with Pathologically Confirmed Dementia with Lewy Bodies

Background: Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia affecting the elderly. The GGGGCC hexanucleotide expansion mutation at the C9orf72 locus has been identified as a major cause of amyotrophic lateral sclerosis and frontotemporal dementia, raising the question of whether this mutation is a factor in DLB. Furthermore, a small number of clinically diagnosed DLB patients have previously been reported to carry the pathologic C9orf72 hexanucleotide repeat expansion. Objective: To explore whether the C9orf72 mutation is present in pathologically confirmed DLB patients. Methods: We screened a cohort of 111 definite DLB cases with extensive Lewy body pathology for the C9orf72 hexanucleotide repeat expansion using the repeat-primed polymerase chain reaction assay. Results: No pathogenic expansions of the C9orf72 hexanucleotide repeat were found, suggesting that there is no causal relationship between C9orf72 and DLB. Conclusion: Our data illustrate that C9orf72 screening of clinically diagnosed DLB patients should only be considered in cases with a family history of motor neuron disease or frontotemporal dementia to distinguish between mimic diseases.

Onset and Remission of Psychosis in Parkinson's Disease: Pharmacologic and Motoric Markers

Psychosis is among the most disabling complications of Parkinsons disease (PD). The chronicity of PD psychosis remains understudied, and the relative importance of dopaminergic therapy versus the disease process itself in engendering psychosis remains unclear. The objective of this study was to examine pharmacologic and motoric correlates of PD psychosis onset and remission in a longitudinally monitored PD cohort.

Dopamine transporter availability reflects gastrointestinal dysautonomia in early Parkinson disease

BACKGROUND Constipation is a prodromal feature of Parkinsons disease (PD) and the gastrointestinal (GI) tract is implicated in the pathogenesis of PD. However, no studies have demonstrated ante-mortem relationships between nigrostriatal dysfunction and GI dysautonomia in PD. METHODS The Scale for Outcomes in Parkinsons disease for Autonomic Symptoms (SCOPA-AUT) assesses dysautonomia in the multi-center Parkinsons Progression Marker Initiative (PPMI). We used linear mixed-effects models and reliable change indices (RCIs) to examine longitudinal associations between dysautonomia and dopamine transporter (DAT) striatal binding ratios (SBRs) measured by single-photon emission computerized tomography in PPMI participants over four years (n = 397 at baseline). RESULTS Adjusted mixed-models of longitudinal data showed that constipation-but not orthostatic hypotension or urinary dysfunction-was associated with reduced SBR in both caudate (P < 0.001) and putamen (P = 0.040). In both regions, SBR reductions between baseline and 4-year follow-up were significant and measurable (P < 0.0001), with larger decline and variance in the caudate nucleus. Four-year change in caudate-but not putaminal-SBR was significantly associated with RCI-indicated progression of GI dysautonomia (P = 0.031), but not other types of dysautonomia. These associations remained after adjusting for the use of medications or supplements to control constipation. Consistent with prior PPMI reports, motor impairment progression was not associated with SBR reduction. CONCLUSIONS GI dysautonomia correlates with reductions in DAT availability; constipation is most closely associated with caudate-DAT reduction. Worsening GI-dysautonomia and reduced bowel movements may accompany advancing nigral degeneration or changes in nigrostriatal dopamine function.

Teaching NeuroImages: Occlusion of all 4 major extracranial vessels

A 68-year-old man presented with 5 weeks of recurrent syncope and vision loss. He had orthostatic hypotension with a blood pressure drop from 145/44 mm Hg sitting to 90/40 mm Hg standing. Neurologic examination and brain MRI were normal. Angiography revealed bilateral internal carotid and vertebral …