Stephan J. Schreiber

No Cerebrocervical Venous Congestion in Patients with Multiple Sclerosis

Multiple sclerosis (MS) is characterized by demyelination centered around cerebral veins. Recent studies suggested this topographic pattern may be caused by venous congestion, a condition termed chronic cerebrospinal venous insufficiency (CCSVI). Published sonographic criteria of CCSVI include reflux in the deep cerebral veins and/or the internal jugular and vertebral veins (IJVs and VVs), stenosis of the IJVs, missing flow in IJVs and VVs, and inverse postural response of the cerebral venous drainage.

Postural dependency of the cerebral venous outflow

We have shown that predominance of the jugular veins in cerebrovenous drainage is limited to the supine position. In the erect position, the vertebral venous system represents the major outflow pathway.

Long-Chain Omega-3 Fatty Acids Improve Brain Function and Structure in Older Adults

Higher intake of seafish or oil rich in long-chain omega-3 polyunsaturated fatty acids (LC-n3-FA) may be beneficial for the aging brain. We tested in a prospective interventional design whether high levels of supplementary LC-n3-FA would improve cognition, and addressed potential mechanisms underlying the effects. Sixty-five healthy subjects (50-75 years, 30 females) successfully completed 26 weeks of either fish oil (2.2 g/day LC-n3-FA) or placebo intake. Before and after the intervention period, cognitive performance, structural neuroimaging, vascular markers, and blood parameters were assayed. We found a significant increase in executive functions after LC-n3-FA compared with placebo (P = 0.023). In parallel, LC-n3-FA exerted beneficial effects on white matter microstructural integrity and gray matter volume in frontal, temporal, parietal, and limbic areas primarily of the left hemisphere, and on carotid intima media thickness and diastolic blood pressure. Improvements in executive functions correlated positively with changes in omega-3-index and peripheral brain-derived neurotrophic factor, and negatively with changes in peripheral fasting insulin. This double-blind randomized interventional study provides first-time evidence that LC-n3-FA exert positive effects on brain functions in healthy older adults, and elucidates underlying mechanisms. Our findings suggest novel strategies to maintain cognitive functions into old age.

Internal jugular vein valve incompetence and intracranial venous anatomy in transient global amnesia

Background: Recently a causal relation between internal jugular vein valve incompetence (IJVVI) and transient global amnesia (TGA) has been suggested. IJVVI is postulated to provoke a transient mesiotemporal ischaemia by venous congestion. This mechanism requires a patent venous pathway from the affected IJV through the transverse sinus, confluens, straight sinus (SS), vein of Galen into the basal vein of Rosenthal and the internal cerebral veins. Objective: To study IJVVI in TGA patients in relation to the intracranial venous anatomy. Methods: IJVVI was defined if a repeated Valsalva manoeuvre (VM) led to a retrograde jugular flow detected by extracranial duplex ultrasound. Non-contrast venous MR angiography (MRA) was performed to analyse intracranial drainage patterns of the SS in relation to the side of the IJVVI. SS drainage was differentiated into three groups: predominantly right, left, and bilateral drainage. Ultrasound studies were performed in 25 TGA patients and 85 age matched controls. Twenty patients underwent venous MRA. Results: Sixty eight per cent of patients and 33% of controls showed unilateral or bilateral IJVVI (p  =  0.0025). In 36% of patients a TGA preceding VM was reported. Drainage pattern of SS and side of IJVVI corresponded in five of eight patients (63%) with VM and four of 12 patients without VM (33%, p  =  0.0994). Conclusion: Our study confirms the significantly higher prevalence of IJVVI in TGA patients. However, no specific IJVVI related intracranial venous drainage patterns could be found to further support the hypothesis of a direct causal relation between IJVVI and TGA.

Brain parenchyma sonography and 123I‐FP‐CIT SPECT in Parkinson's disease and essential tremor

We aimed to investigate the accuracy of transcranial brain parenchyma sonography (TCS) for differentiation between idiopathic Parkinsons disease (PD) and essential tremor (ET) in comparison to 123I‐FP‐CIT SPECT (FP‐CIT SPECT). Seventy‐four patients, in whom PD or ET was suspected on the basis of clinical criteria, were analyzed. The echogenicity of the substantia nigra (SN) and the striatal binding of dopamine transporters (DAT) were evaluated by TCS and FP‐CIT SPECT, respectively. Three patients were excluded due to an insufficient transtemporal bone window using TCS. Forty‐six and 25 patients were clinically classified as PD and ET. SPECT revealed a reduced DAT binding in 42 of all 71 included patients. Thirty‐six of the 42 patients with abnormal FP‐CIT SPECT findings had a pathological SN hyperechogenicity, whereas TCS findings in the remaining 6 patients were normal. In 27 of 29 patients with normal SPECT findings the SN echogenicity was regular. Referring to FP‐CIT SPECT, the sensitivity and specificity of TCS for detection of PD were 86 and 93%; the positive and negative predictive values were 95 and 82%, respectively. Sensitivity and specificity in detection of clinically diagnosed PD patients were 78 and 92% for TCS and 91 and 100% for FP‐CIT SPECT, respectively. In patients with pathological FP‐CIT SPECT and pathological TCS, the extent of SN hyperechogenicity did not correlate with the degree of reduction in dopamine transporter binding on the side opposite of the more affected limb. TCS allows a reliable differentiation of PD and ET. The TCS SN hyperechogenicity does not correlate with the extent of dopaminergic neuron degeneration.

Venous drainage in multiple sclerosis A combined MRI and ultrasound study

Background: Chronic cerebrospinal venous insufficiency (CCSVI) was proposed as the causal trigger for developing multiple sclerosis (MS). However, current data are contradictory and a gold standard for venous flow assessment is missing. Objective: To compare structural magnetic resonance venography (MRV) and dynamic extracranial color-coded duplex sonography (ECCS) in a cohort of patients with MS. Methods: We enrolled 40 patients (44 ± 10 years). All underwent contrast-enhanced MRV for assessment of internal jugular vein (IJV) and azygos vein (AV) narrowing, graded into 3 groups: 0%–50%, 51%–80%, and >80%. ECCS analysis of blood flow direction, cross-sectional area (CSA), and blood volume flow (BVF) in both IJV and vertebral veins (VV) occurred in the supine and upright body position. Results: MRV identified 1 AV narrowing. IJV analysis yielded 12 patients for group 1 (30%), 19 patients for group 2 (48%), and 9 patients for group 3 (22%). By ECCS criteria, 4 patients (10%) presented with venous drainage abnormalities. Jugular BVF was different only between groups 1 and 3 (616 ± 133 vs 381 ± 213 mL/min, p = 0.02). No other parameters in supine position and none of the parameters in the upright body position, apart from the IJV-BVF decrease in groups 1 and 3 (479 ± 172 vs 231 ± 144 mL/min, p = 0.01), were different. Conclusions: Our ECCS data contradict the postulated 100% prevalence of CCSVI criteria in MS. MRV seems more sensitive to detect IJV narrowing compared to ECCS. A measurable hemodynamic effect only exists in vessel narrowings >80%. Our combined data argue against a causal relationship of venous narrowing and MS, favoring the rejection of the CCSVI hypothesis.

Incompetence of internal jugular valve in patients with primary exertional headache: a risk factor?

The pathophysiology of primary exertional headache (EH) is unknown. Physical exertion is associated with Valsalva-like manoeuvres (VM). VM leads to increased intrathoracic pressure and reduces cerebral venous drainage. Internal jugular vein valve incompetence (IJVVI) leads to retrograde venous flow during VM with transient increase of intracranial pressure. We analysed the prevalence of IJVVI in EH patients using duplex ultrasound. Bilateral measurements were performed at rest and during VM in 20 patients and 40 controls. Incompetence was concluded if retrograde venous flow could be seen in the jugular Doppler spectrum during repeated VM. Seventy percent of EH patients and 20% of controls demonstrated IJVVI, yielding a significant difference (P = 0.0004). IJVVI was always observed on the dominant venous drainage side. Our study suggests that intracranial venous congestion caused by retrograde jugular venous flow might play a role in the pathophysiology of EH with IJVVI as a risk factor.

What Went Wrong? the Flawed Concept of Cerebrospinal Venous Insufficiency:

In 2006, Zamboni reintroduced the concept that chronic impaired venous outflow of the central nervous system is associated with multiple sclerosis (MS), coining the term of chronic cerebrospinal venous insufficiency (‘CCSVI’). The diagnosis of ‘CCSVI’ is based on sonographic criteria, which he found exclusively fulfilled in MS. The concept proposes that chronic venous outflow failure is associated with venous reflux and congestion and leads to iron deposition, thereby inducing neuroinflammation and degeneration. The revival of this concept has generated major interest in media and patient groups, mainly driven by the hope that endovascular treatment of ‘CCSVI’ could alleviate MS. Many investigators tried to replicate Zambonis results with duplex sonography, magnetic resonance imaging, and catheter angiography. The data obtained here do generally not support the ‘CCSVI’ concept. Moreover, there are no methodologically adequate studies to prove or disprove beneficial effects of endovascular treatment in MS. This review not only gives a comprehensive overview of the methodological flaws and pathophysiologic implausibility of the ‘CCSVI’ concept, but also summarizes the multimodality diagnostic validation studies and open-label trials of endovascular treatment. In our view, there is currently no basis to diagnose or treat ‘CCSVI’ in the care of MS patients, outside of the setting of scientific research.

Migraine aggravation caused by cephalic venous congestion

Background.—Cerebral venous distension is thought by some to serve as a source of migraine pain. Previous investigators have tried to modify pain intensity by induction of additional venous congestion via compression of both internal jugular veins (Queckenstedts maneuver). The magnitude of blood flow within the internal jugular veins depends markedly on body position, and inconsistencies in positioning may have influenced their results.

GABAB receptor antibodies in paraneoplastic cerebellar ataxia.

Autoantibodies to the gamma-aminobutyric acid-B (GABAB) receptor were recently described in patients with limbic encephalitis presenting with early or prominent seizures. We report on a 64-year-old man with malignant melanoma who during adjuvant therapy with interferon (IFN)-alpha developed cerebellar ataxia. Indirect immunofluorescence on brain tissue sections revealed high-titer (1:20,000) IgG1 serum autoantibodies to the cerebellar molecular and granular layer, which were confirmed to be directed against GABAB receptor in a cell-based assay. This case highlights cerebellar ataxia in the absence of seizures as a clinical manifestation of GABAB receptor autoimmunity and extends the spectrum of tumors underlying this condition to malignant melanoma. IFN-alpha therapy may have contributed to the development of autoimmunity in this patient.