Neuroimaging Pearls from the MDS Congress Video Challenge. Part 2: Acquired Disorders.

The MDS Video Challenge continues to be the one of most widely attended sessions at the International Congress. Although the primary focus of this event is the presentation of complex and challenging cases through videos, a number of cases over the years have also presented an unusual or important neuroimaging finding related to the case. We reviewed the previous Video Challenge cases and present here a selection of those cases which incorporated such imaging findings. We have compiled these "imaging pearls" into two anthologies. The first focuses on pearls where the underlying diagnosis was a genetic condition. This second anthology focuses on imaging pearls in cases where the underlying condition was acquired. For each case we present brief clinical details along with neuroimaging findings, the characteristic imaging findings of that disorder and, finally, the differential diagnosis for the imaging findings seen.

Metabolomic analysis data of MPP+-exposed SH-SY5Y cells using CE-TOFMS.

1-Methyl-4-phenylpyridinium (MPP+)-treated human neuroblastoma SH-SY5Y cells have been generally accepted as a cellular model for Parkinson's disease. This article contains metabolic analysis data of not only cell lysate but also culture supernatants to understand comprehensive metabolic disturbances in this model. Metabolic analysis employed by capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). Data obtained by CE-TOFMS were processed to extract peak information including m/z, peak area, and migration time. The data provided in this manuscript have been analyzed and discussed in the research article entitled "Metabolomic analysis revealed mitochondrial dysfunction and aberrant choline metabolism in MPP+-exposed SH-SY5Y cells" [1].

Metabolomic analysis revealed mitochondrial dysfunction and aberrant choline metabolism in MPP+-exposed SH-SY5Y cells.

1-Methyl-4-phenylpyridinium (MPP+)-treated human neuroblastoma SH-SY5Y cells have been generally accepted as a cellular model for Parkinson's disease. To understand comprehensive metabolic disturbances in this model, both cell lysates and culture supernatants were subjected to metabolomic analysis. As expected from the fact that MPP+ inhibits mitochondrial complex I, a metabolic shift from mitochondrial oxidative phosphorylation to glycolysis was indicated by an increase in extracellular lactic acid and a parallel depletion of pyruvic acid. In cell lysates, the metabolic shift was supported by consistent decreases in TCA cycle intermediates. Metabolomic analysis also revealed aberrant choline metabolism. Choline in the culture supernatant was elevated 8.5- and 17-fold by 30 and 300 µM MPP+ exposure, respectively; therefore, extracellular choline might be a metabolic biomarker for Parkinson's disease.

A metabolic profile of polyamines in parkinson disease: A promising biomarker.

OBJECTIVE: Aging is the highest risk factor for Parkinson disease (PD). Under physiological conditions, spermidine and spermine experimentally enhance longevity via autophagy induction. Accordingly, we evaluated the ability of each polyamine metabolite to act as an age-related, diagnostic, and severity-associated PD biomarker. METHODS: Comprehensive metabolome analysis of plasma was performed in Cohort A (controls, n = 45; PD, n = 145), followed by analysis of 7 polyamine metabolites in Cohort B (controls, n = 49; PD, n = 186; progressive supranuclear palsy, n = 19; Alzheimer disease, n = 23). Furthermore, 20 patients with PD who were successively examined within Cohort B were studied using diffusion tensor imaging (DTI). Association of each polyamine metabolite with disease severity was assessed according to Hoehn and Yahr stage (H&Y) and Unified Parkinson's Disease Rating Scale motor section (UPDRS-III). Additionally, the autophagy induction ability of each polyamine metabolite was examined in vitro in various cell lines. RESULTS: In Cohort A, N8-acetylspermidine and N-acetylputrescine levels were significantly and mildly elevated in PD, respectively. In Cohort B, spermine levels and spermine/spermidine ratio were significantly reduced in PD, concomitant with hyperacetylation. Furthermore, N1,N8-diacetylspermidine levels had the highest diagnostic value, and correlated with H&Y, UPDRS-III, and axonal degeneration quantified by DTI. The spermine/spermidine ratio in controls declined with age, but was consistently suppressed in PD. Among polyamine metabolites, spermine was the strongest autophagy inducer, especially in SH-SY5Y cells. No significant genetic variations in 5 genes encoding enzymes associated with spermine/spermidine metabolism were detected compared with controls. INTERPRETATION: Spermine synthesis and N1,N8-diacetylspermidine may respectively be useful diagnostic and severity-associated biomarkers for PD. ANN NEUROL 2019;86:251-263.

Serum caffeine and metabolites are reliable biomarkers of early Parkinson disease.

OBJECTIVE: To investigate the kinetics and metabolism of caffeine in serum from patients with Parkinson disease (PD) and controls using liquid chromatography-mass spectrometry. METHODS: Levels of caffeine and its 11 metabolites in serum from 108 patients with PD and 31 age-matched healthy controls were examined by liquid chromatography-mass spectrometry. Mutations in caffeine-associated genes were screened by direct sequencing. RESULTS: Serum levels of caffeine and 9 of its downstream metabolites were significantly decreased even in patients with early PD, unrelated to total caffeine intake or disease severity. No significant genetic variations in CYP1A2 or CYP2E1, encoding cytochrome P450 enzymes primarily involved in metabolizing caffeine in humans, were detected compared with controls. Likewise, caffeine concentrations in patients with PD with motor complications were significantly decreased compared with those without motor complications. No associations between disease severity and single nucleotide variants of the ADORA2A gene encoding adenosine 2A receptor were detected, implying a dissociation of receptor sensitivity changes and phenotype. The profile of serum caffeine and metabolite levels was identified as a potential diagnostic biomarker by receiver operating characteristic curve analysis. CONCLUSION: Absolute lower levels of caffeine and caffeine metabolite profiles are promising diagnostic biomarkers for early PD. This is consistent with the neuroprotective effect of caffeine previously revealed by epidemiologic and experimental studies. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that decreased serum levels of caffeine and its metabolites identify patients with PD.

Limb-Shaking Transient Ischemic Attack Induced by Middle Cerebral Artery Dissection after Lung Surgery.

We report a case of limb-shaking transient ischemic attack (TIA) caused by a dissection of the middle cerebral artery (MCA) following lung surgery under general anesthesia. An 81-year-old male patient who underwent lobectomy for lung cancer suddenly developed transient shaking movements of the neck and the left upper distal limb on postoperative day 1. On the basis of the double-barrel appearance of the right M1 segment of the MCA, a diagnosis of MCA dissection was made. Physicians should be aware that limb-shaking TIA is sometimes caused by MCA dissection and could be precipitated by any condition, including lung surgery under general anesthesia.

Spontaneous spinal subarachnoid hemorrhage after severe coughing: a case report.

INTRODUCTION: Spinal subarachnoid hemorrhage has many causes including trauma, vascular malformations, aneurysms, spinal cord tumors, coagulation abnormalities, use of anticoagulants, systemic lupus erythematosus, or Behçet's disease. We report on a rare case of a spontaneous spinal subarachnoid hemorrhage after severe coughing of unknown origin. To the best of our knowledge, this is the first report of spontaneous spinal subarachnoid hemorrhage after severe coughing. CASE PRESENTATION: A 66-year-old Japanese woman initially complained of headache with severe back pain after severe coughing. She was referred to our neurology department 6 days after her first visit to our hospital. No neurological deficits were revealed except for meningism. Computed tomography of her head revealed no abnormality. A lumbar puncture showed bloody cerebrospinal fluid with xanthochromia. Cerebral angiography revealed no abnormality. Magnetic resonance imaging of her lumbar spine revealed subarachnoid hemorrhage. Spinal angiography revealed no abnormality. The diagnosis of spontaneous spinal subarachnoid hemorrhage was made. She recovered with conservative treatment and her neurological status was normal 2 years after the onset. CONCLUSIONS: Spontaneous spinal subarachnoid hemorrhage could be caused by rapid changes in intrathoracic and intra-abdominal pressure. Spontaneous subarachnoid hemorrhage should be considered when sudden back pain associated with severe headache develops. Even though emergent surgical decompression is necessary when the neurological state progressively deteriorates, conservative treatment with close monitoring of the symptoms can be recommended for patients with a stable neurological status.

Longitudinally extensive transverse myelitis with intramedullary metastasis of small-cell lung carcinoma: an autopsy case report.

Background. Longitudinally extensive transverse myelitis (LETM) is characterized by spinal cord inflammation extending vertically through three or more vertebral segments. The widespread use of MRI revealed LETM more frequency than ever. We report the case of a patient with pathologically confirmed small-cell lung carcinoma metastasis into the spinal cord presenting as LETM. Case Presentation. A 74-year-old man developed rapidly progressive sensorimotor disturbance and vesicorectal dysfunction. T2-weighted magnetic resonance imaging of the spine revealed LETM at the level of from T3 to conus medullaris; gadolinium enhancement showed concurrent tumor in the thoracic spinal cord from T10 to T11. Systemic survey identified a nodular mass in the lung that was verified as small-cell carcinoma. Following initial failed treatment by high-dose steroid, the patient underwent an emergent microsurgical tumor resection. Histological examination was identical with the lung carcinoma. The patient died of tumor progression at the 47th day after admission. At autopsy, only changes of edema were found in the gray matter of the cord, while tumor cells were not noted in it. Conclusion. Metastasis may rarely present symptoms of LETM. Prompt identification of underlying etiology by contrast examination and systemic survey is crucial for the patient assumed as LETM.