Spinal cord and infratentorial lesions in radiologically isolated syndrome are associated with decreased retinal ganglion cell/inner plexiform layer thickness.

BACKGROUND: The role of retinal imaging with optical coherence tomography (OCT) in assessing individuals with radiologically isolated syndrome (RIS) remains largely unexplored. OBJECTIVE: To assess retinal layer thicknesses in RIS and examine their associations with clinical features suggestive of increased risk for conversion to multiple sclerosis (MS). METHODS: A total of 30 RIS subjects and 60 age- and sex-matched healthy controls (HC) underwent retinal imaging with spectral-domain OCT, followed by automated segmentation of retinal layers. RESULTS: Overall, retinal layer thicknesses did not differ between RIS and HC. However, RIS subjects with spinal cord (SC) lesions had lower ganglion cell + inner plexiform layer (GCIP) thickness compared to HC (-4.41 µm; p = 0.007) and RIS without SC lesions (-3.53 µm; p = 0.041). Similarly, RIS subjects with infratentorial (IT) brain lesions had lower GCIP thickness compared to HC (-4.07 µm; p < 0.001) and RIS without IT lesions (-3.49 µm; p = 0.029). Multivariate analyses revealed that the presence of SC or IT lesions were independently associated with lower GCIP thickness in RIS (p = 0.04 and p = 0.03, respectively). Other patient characteristics, including sex, abnormal cerebrospinal fluid, and presence of gadolinium-enhancing or juxtacortical lesions, were not associated with retinal layer thicknesses. CONCLUSION: The presence of SC or IT lesions in RIS may be associated with retinal neuro-axonal loss, supporting the presence of more disseminated disease.

Transcranial Doppler Changes in Patients Treated with Extracorporeal Membrane Oxygenation.

BACKGROUND: Transcranial Doppler (TCD) has significant implications for neurovascular assessment in patients being treated with venoarterial-extracorporeal membrane oxygenation (VA-ECMO). However, there have been no studies demonstrating the changes in pulsatility indices (PIs) seen in these patients. Nonpulsatile waveforms are seen during on-pump coronary artery bypass graft, but low or low-normal PIs have never been reported. It is important to be aware of these changes, as they can be misinterpreted as cerebral vasodilation, vasoconstriction, increased intracranial pressures (ICPs), or cerebral circulatory arrest. METHODS: Data from 11 TCDs from 8 patients on VA-ECMO in the Cedars Sinai Medical Center Cardiac Surgical Intensive Care Unit were reviewed. Mean pulsatility indices were calculated for each patient using Gosling's PI formula. The values obtained were correlated with ejection fraction (EF) values obtained from a transthoracic or transesophageal echocardiogram. RESULTS: PIs were globally low or absent in all 11 TCDs. In 3 patients, TCDs were performed at the initiation and conclusion of the VA-ECMO cannulation. The PI values for these TCDs correlated directly with changes in EFs. Also, an abrupt rise in PI to normal value was seen with the placement of a total artificial heart and the return of pulsatile circulation. CONCLUSIONS: We demonstrate that PIs on TCDs in patients treated with VA-ECMO are either low or cannot be calculated depending on the severity of myocardial suppression, and should not be mistaken for cerebral vasodilation or cerebral circulatory arrest. Moreover, rising PIs in these patients can represent improving cardiac function and should not be confused with elevated ICPs.

Diagnosis influences response of cerebral near infrared spectroscopy to intracranial hypertension in children.

OBJECTIVE: To describe cerebral regional oxygen saturation measured by near infrared spectroscopy in the setting of normal and increased intracranial pressure in children to evaluate the association between cerebral regional oxygen saturation and intracranial pressure in comparison with other clinical variables. DESIGN: Prospective observational cohort study. SETTING: Two academic tertiary care centers' pediatric intensive care units. PATIENTS: Thirty patients with intracranial pressure and near infrared spectroscopy monitoring (median age, 11.5 yrs; interquartile range, 5.2-13 yrs) for a range of neurologic diagnoses, including brain tumor, trauma, intracerebral hemorrhage, and hydrocephalus. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Temporally correlated cerebral regional oxygen saturation with hematologic (hematocrit), biochemical (pH), and physiological (intracranial pressure, mean arterial pressure, cerebral perfusion pressure, temperature, heart rate, pulse oximetry and end-tidal carbon dioxide) variables. Cerebral regional oxygen saturation during episodes of increased intracranial pressure was lower than with normal intracranial pressure (mean +/- sd intracranial pressure >20 = 71% +/- 13% vs. intracranial pressure <20 = 75% +/- 10%), although the mean difference (-4%) is small compared with variability in the measurement. Neither isolated values nor change in cerebral regional oxygen saturation were significantly associated with intracranial pressure or cerebral perfusion pressure in the overall population. Isolated values and change in end-tidal CO2 were significantly correlated with cerebral regional oxygen saturation and change in cerebral regional oxygen saturation (all p < 0.01). In exploratory analyses, the diagnostic group significantly modified the effect of intracranial hypertension on regional oxygen saturation: regional oxygen saturation decreased during intracranial hypertension in patients with brain tumors (p = .05) and hydrocephalus (p < .001) but increased during intracranial hypertension in those with intracranial hemorrhage (p < .001). CONCLUSIONS: These data suggest that cerebral regional oxygen saturation is lower with intracranial hypertension. However, the relationship between cerebral regional oxygen saturation and intracranial pressure is strongly influenced by diagnosis.

Improvement of stiff-person syndrome symptoms in pregnancy: Case series and literature review.

OBJECTIVE: To describe 2 cases from a single academic institution of improvement in stiff-person syndrome (SPS) symptoms during pregnancy and to review the clinical outcomes of SPS in 6 additional pregnancies described in the literature. METHODS: Evaluation of clinical symptoms and treatment changes of disease state during pregnancy. RESULTS: Seven patients with 9 pregnancies are described in women with a diagnosis of SPS. Six of 7 (86%) women were positive for glutamic acid decarboxylase (GAD65) antibody. In 5 of 9 (56%) pregnancies, symptomatic medications (antispasmodics) were significantly reduced with stabilization or improvement in symptoms through pregnancy. Nine live, healthy pregnancies resulted. All 7 (100%) women experienced worsening of symptoms after the birth of their children, and symptomatic therapies were resumed and/or increased. CONCLUSIONS: The immune pathogenesis of SPS continues to be explored. Immunomodulatory shifts during pregnancy may influence changes of clinical SPS symptoms and provide insight into the unique pathogenesis of SPS. Some women with SPS may be able to reduce symptomatic medications related to clinical improvement during pregnancy. Women with SPS may safely carry pregnancies to term, delivering healthy and unaffected babies.

CADASIL vs. Multiple Sclerosis: Is It Misdiagnosis or Concomitant? A Case Series.

Introduction: Cerebral autosomal dominant arteriopathy and subcortical infarct leukoencephalopathy (CADASIL) is the most common form of hereditary stroke caused by a mutation in the NOTCH3 gene located on the short arm of chromosome 19. A small number of published reports describe CADASIL patients who were initially diagnosed as multiple sclerosis. Although it was previously indicated that there was no association between NOTCH3 mutations and multiple sclerosis, the involvement of autoimmune mechanisms among patients with CADASIL has been hypothesized. Case Presentation: Case 1 is a middle-aged woman with initial diagnoses of multiple sclerosis (MS) and myelitis that continued to progress despite treatment with disease-modifying agents. She had occasional migraines, transient blurred vision, and multiple lacunar infarcts. She continued treatment for about 15 years with no significant alleviation and progressive changes on brain MRI; genetic testing was ordered which showed NOTCH3 mutation, and diagnosis was changed to CADASIL with subsequent revision of treatment course. However, the presence of myelitis in this patient is unusual and may raise the question of a concurrent autoimmune process. Case 2 is a woman presenting with vertigo and paresthesia and diagnosed with MS based on an initial brain MRI showing biventricular white matter hyperintensities; however, she was not started on any disease-modifying agents. Her symptoms were reevaluated by a neurologist, and genetic testing was performed for NOTCH 3. Case 3 is a young woman with a history of migraines who initially presented with numbness and gait ataxia which later progressed to speech difficulty and memory loss. A diagnosis of MS was established which was later changed to CADASIL. Conclusion: Since CADASIL is a rare disease, it is imperative to raise awareness of its unique clinical condition as well as variation in its clinical presentations. It is crucial that the overlapping symptoms between MS and CADASIL be thoroughly examined to avoid misdiagnosis and treatment complications. The involvement of autoimmune mechanisms in CADASIL and the role of NOTCH3 gene mutations in provoking an autoimmune process should be further investigated.