Spinal cord motion and CSF flow in the cervical spine of 70 healthy participants.

Pulsatile spinal cord and CSF velocities related to the cardiac cycle can be depicted by phase-contrast MRI. Among patients with spontaneous intracranial hypotension, we have recently described relevant differences compared with healthy controls in segment C2/C3. The method might be a promising tool to solve clinical and diagnostic ambiguities. Therefore, it is important to understand the physiological range and the effects of clinical and anatomical parameters in healthy volunteers. Within a prospective study, 3D T2 -weighted MRI for spinal canal anatomy and cardiac-gated phase-contrast MRI adapted to CSF flow and spinal cord motion for time-resolved velocity data and derivatives were performed in 70 participants (age 20-79 years) in segments C2/C3 and C5/C6. Correlations were analyzed by multiple linear regression models; p < 0.01 was required to assume a significant impact of clinical or anatomical data quantified by the regression coefficient B. Data showed that in C2/C3, the CSF and spinal cord craniocaudal velocity ranges were 4.5 ± 0.9 and 0.55 ± 0.15 cm/s; the total displacements were 1.1 ± 0.3 and 0.07 ± 0.02 cm, respectively. The craniocaudal range of the CSF flow rate was 8.6 ± 2.4 mL/s; the CSF stroke volume was 2.1 ± 0.7 mL. In C5/C5, physiological narrowing of the spinal canal caused higher CSF velocity ranges and lower stroke volume (C5/C6 B = +1.64 cm/s, p < 0.001; B = -0.4 mL, p = 0.002, respectively). Aging correlated to lower spinal cord motion (e.g., B = -0.01 cm per 10 years of aging, p < 0.001). Increased diastolic blood pressure was associated with lower spinal cord motion and CSF flow parameters (e.g., C2/C3 CSF stroke volume B = -0.3 mL per 10 mmHg, p < 0.001). Males showed higher CSF flow and spinal cord motion (e.g., CSF stroke volume B = +0.5 mL, p < 0.001; total displacement spinal cord B = +0.016 cm, p = 0.002). We therefore propose to stratify data for age and sex and to adjust for diastolic blood pressure and segmental narrowing in future clinical studies.

Novel homozygous LAMB1 in-frame deletion in a pediatric patient with brain anomalies and cerebrovascular event.

Biallelic pathogenic variants in LAMB1 have been associated with autosomal recessive lissencephaly 5 (OMIM 615191), which is characterized by brain malformations (cobblestone lissencephaly, hydrocephalus), developmental delay, and epilepsy. Pathogenic variants in LAMB1 are rare, with only 11 pathogenic variants and 11 patients reported to date. Here, we report on a 6-year-old patient from a consanguineous family with profound developmental delay, microcephaly, and a history of a perinatal cerebrovascular event. Brain magnetic resonance imaging (MRI) showed cerebellar cystic defects, signal intensity abnormalities, and a hypoplastic corpus callosum. Trio-exome analysis revealed a homozygous in-frame deletion of Exons 23 and 24 of LAMB1 affecting 104 amino acids including the epidermal growth factor (EGF)-like units 11 and 12 in Domain III. To our knowledge, this is the first reported in-frame deletion in LAMB1. Our findings broaden the clinical and molecular spectrum of LAMB1-associated syndromes.

CSF Flow and Spinal Cord Motion in Patients With Spontaneous Intracranial Hypotension: A Phase Contrast MRI Study.

BACKGROUND AND OBJECTIVES: Spontaneous intracranial hypotension (SIH) is characterized by loss of CSF volume. We hypothesize that in this situation of low volume, a larger CSF flow and spinal cord motion at the upper spine can be measured by noninvasive phase contrast MRI. METHODS: A prospective, age-, sex-, and body mass index (BMI)-matched controlled cohort study on patients with SIH presenting with spinal longitudinal extradural fluid collection (SLEC) was conducted from October 2021 to February 2022. Cardiac-gated 2D phase contrast MRI sequences were acquired at segment C2/C3, and C5/C6 for CSF flow, and spinal cord motion analysis. Data processing was fully automated. CSF flow and spinal cord motion were analyzed by peak-to-peak amplitude and total displacement per segment and heartbeat, respectively. Clinical data included age, height, BMI, duration of symptoms, Bern score according to Dobrocky et al., and type of the spinal CSF leak according to Schievink et al. Groups were compared via the Mann-Whitney U test; multiple linear regression analysis was performed to address possible relations. RESULTS: Twenty patients with SIH and 40 healthy controls were analyzed; each group consisted of 70% women. Eleven patients with SIH presented with type 1 leak, 8 with type 2, and 1 was indeterminate. CSF flow per heartbeat was increased at C2/C3 (peak-to-peak amplitude 65.68 ± 18.3 vs 42.50 ± 9.8 mm/s, total displacement 14.32 ± 3.5 vs 9.75 ± 2.7 mm, p < 0.001, respectively). Craniocaudal spinal cord motion per heartbeat was larger at segment C2/C3 (peak-to-peak amplitude 7.30 ± 2.4 vs 5.82 ± 2.0 mm/s, total displacement 1.01 ± 0.4 vs 0.74 ± 0.4 mm, p = 0.006, respectively) and at segment C5/C6 (total displacement 1.41 ± 0.7 vs 0.97 ± 0.4 mm, p = 0.021). DISCUSSION: SLEC-positive patients with SIH show higher CSF flow and higher spinal cord motion at the upper cervical spine. This increased craniocaudal motion of the spinal cord per heartbeat might produce increased mechanical strain on neural tissue and adherent structures, which may be a mechanism leading to cranial nerve dysfunction, neck pain, and stiffness in SIH. Noninvasive phase contrast MRI of CSF flow and spinal cord motion is a promising diagnostic tool in SIH. TRIAL REGISTRATION INFORMATION: German Clinical Trials Register, identification number: DRKS00017351. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that noninvasive phase contrast MRI of the upper spine identifies differences in CSF flow and spinal cord motion in patients with SIH compared with healthy controls.

Spontaneous intracranial hypotension: diagnostic and therapeutic workup.

Spontaneous intracranial hypotension (SIH) is an orthostatic headache syndrome with typical MRI findings among which engorgement of the venous sinuses, pachymeningeal enhancement, and effacement of the suprasellar cistern have the highest diagnostic sensitivity. SIH is in almost all cases caused by spinal CSF leaks. Spinal MRI scans showing so-called spinal longitudinal extradural fluid (SLEC) are suggestive of ventral dural tears (type 1 leak) which are located with prone dynamic (digital subtraction) myelography. As around half of the ventral dural tears are located in the upper thoracic spine, additional prone dynamic CT myelography is often needed. Leaking nerve root sleeves typically associated with meningeal diverticulae (type 2 leaks) and CSF-venous fistulas (type 3 leaks) are proven via lateral decubitus dynamic digital subtraction or CT myelography: type 2 leaks are SLEC-positive if the tear is proximal and SLEC-negative if it is distal, and type 3 leaks are always SLEC-negative. Although 30-70% of SIH patients show marked improvement following epidural blood patches applied via various techniques definite cure mostly requires surgical closure of ventral dural tears and surgical ligations of leaking nerve root sleeves associated with meningeal diverticulae or CSF-venous fistulas. For the latter, transvenous embolization with liquid embolic agents via the azygos vein system is a novel and valuable therapeutic alternative.

Emphysema- and airway-dominant COPD phenotypes defined by standardised quantitative computed tomography.

EvA (Emphysema versus Airway disease) is a multicentre project to study mechanisms and identify biomarkers of emphysema and airway disease in chronic obstructive pulmonary disease (COPD). The objective of this study was to delineate objectively imaging-based emphysema-dominant and airway disease-dominant phenotypes using quantitative computed tomography (QCT) indices, standardised with a novel phantom-based approach.441 subjects with COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages 1-3) were assessed in terms of clinical and physiological measurements, laboratory testing and standardised QCT indices of emphysema and airway wall geometry.QCT indices were influenced by scanner non-conformity, but standardisation significantly reduced variability (p<0.001) and led to more robust phenotypes. Four imaging-derived phenotypes were identified, reflecting "emphysema-dominant", "airway disease-dominant", "mixed" disease and "mild" disease. The emphysema-dominant group had significantly higher lung volumes, lower gas transfer coefficient, lower oxygen (PO2 ) and carbon dioxide (PCO2 ) tensions, higher haemoglobin and higher blood leukocyte numbers than the airway disease-dominant group.The utility of QCT for phenotyping in the setting of an international multicentre study is improved by standardisation. QCT indices of emphysema and airway disease can delineate within a population of patients with COPD, phenotypic groups that have typical clinical features known to be associated with emphysema-dominant and airway-dominant disease.

Severe disease reactivation in four patients with relapsing-remitting multiple sclerosis after fingolimod cessation.

OBJECTIVES: Fingolimod is a well-established, highly effective immunomodulatory treatment for patients with relapsing-remitting multiple sclerosis (RRMS). However, little is known about disease course after its discontinuation. METHODS: This is a case series on four patients with RRMS who had a severe reactivation after fingolimod discontinuation. RESULTS: One patient had pretreatment with glatiramer acetate, interferon-ß 1b and interferon-ß 1a and another with interferon-ß 1a, intravenous immunoglobulins and natalizumab whereas the other two were therapy naïve before fingolimod initiation. Patients were treated with fingolimod for two, thirty, forty-five and seventy-eight months, respectively. Fingolimod had to be discontinued because of persisting lymphopenia, severe varicella zoster virus infection, subarachnoid hemorrhage, and increased liver function enzymes, respectively. Between two to four months after fingolimod cessation these patients had a severe relapse. Cerebral magnetic resonance imaging (MRI) at this point revealed multiple new lesions, partially with contrast ring enhancement. Partial recovery was achieved after steroid pulse therapy followed by plasma exchange in two patients. CONCLUSIONS: Despite the limited evidence from our case series on potential disease reactivation exceeding pre-fingolimod activity in a subgroup of RRMS patients, particularly patients with previously high disease activity should undergo frequent clinical as well as radiological monitoring after fingolimod discontinuation.