On 2016 Dec 20, Alessandro Rasman commented:

Anatomical stenosis of the internal jugular veins : supportive evidence of chronic cerebrospinal venous insufficiency ?

Andrea Baiocchini, MD Raffaele Toscano, Wilfredo von Lorch and Franca Del Nonno National Institute for Infectious Diseases "L. Spallanzani", Via Portuense 292, 00149 Rome, Italy, +390655170277, Fax +390655170430

We write in relation to the editorial commentary from Khan et Tselis (1) who rightly suggest caution to consider chronic cerebrospinal venous insufficiency (CCSVI) as a pathological entity and cast serious doubt on its relevance to multiple sclerosis (MS); they forecast properly designed studies to investigate the relevance of CCSVI to MS, in order to carry out interventional procedures.

The absence of extracranial venous stenosis at the earliest stage of MS makes it an unlikely cause of the disease (2). The idea of venous congestion as a possible contributor to the pathogenesis of MS has been discussed for the past 40 years, but remained widely unappreciated by the scientific community.

In contrast with other authors, Zamboni et al (3) defined CCSVI as a vascular condition associated with MS; it is characterized by multiple intraluminal stenosing malformations of the principal pathways of extracranial venous drainage, particularly in the internal jugular veins (IJVs) and the azygous vein (AZY), that restrict the normal outflow of blood from the brain. In the study of Zamboni et al there was significant extracranial venous stenosis localised at the principal level of the cerebrospinal venous segments as detected by selective venography and anomalies of venous outflow at color Doppler high resolution examination. The pathological consequences of CCSVI have been hypothesised to emanate from chronic venous reflux and hypertension leading to increased iron deposition in the brain and subsequent MS pathology, including inflammation and neurodegeneration.

Other recent reports found no differences in cerebrospinal venous drainage using transcranial and extracranial Doppler imaging (4-5). The discrepancies in the results may be explained with the absence of standardized internationally accepted criteria for normal Doppler venous flow parameters (2).

We performed complete post-mortem examination of two patients with MS, died for different causes. One patient, a 74 year-old-woman, was hospitalized for acute respiratory illness and died because of bacterial pneumonia; the other one, a 35 year-old-woman, died for otogenic bacterial meningitis complicated with internal jugular thrombosis as demonstrated on MR venography.

Postmortem examination demonstrated in both patients a marked stenosis of left internal jugular vein at the apex of the angle formed by the two heads of the sternocleidomastoid muscle where the IJV overlie the carotid artery with ectasia and congestion of the intracranial veins. Venous flow slowing, caused by the stenosis, had predisposed to IJV thrombosis, histologically demonstrated in the second case.

Severe inflammatory disease may be a risk factor for deep venous thrombosis but also chronic cerebrospinal venous insufficiency. We demonstrate, for the first time as far as we are aware, the presence of anatomical alteration in the veins of the neck with impaired venous drainage from the central nervous system in two patients with multiple sclerosis who died from other causes.

We do not know the exact implications in MS pathology and certainly there is no doubt that this area warrants a great deal more study. Clinical trials for evaluating new therapeutic agents and other clinical experimental protocols may be required.

References: 1. Khan O, Tselis A. Chronic cerebrospinal venous insufficiency and multiple sclerosis: science or science fiction? J Neurol Neurosurg Psychiatry 2011;82:355. 2. Yamout B, Herlopian A, Issa Z Extracranial venous stenosis is an unlikely cause of multiple sclerosis Mult Scler 2010 16: 1341-9 3. Zamboni P, Galeotti R, Menegatti E, et al Chronic cerebrospinal venous insuffiency in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 2009;80:392-9. 4. Doepp F, Paul F, Valdueza JM, et al No cerebrocervical venous congestion in patients with multiple sclerosis. Ann Neurol 2010, 68:173-183. 5. Sundstrom P, Wahlin A, Ambarki K, et al Venous and cerebrospinal fluid flow in multiple sclerosis: a case-control study. Ann Neurol 2010, 68:255-259.

Conflict of Interest: None declared

Published 28 April 2011

On 2016 Dec 20, Alessandro Rasman commented:

Anatomical stenosis of the internal jugular veins : supportive evidence of chronic cerebrospinal venous insufficiency ?

Andrea Baiocchini, MD Raffaele Toscano, Wilfredo von Lorch and Franca Del Nonno National Institute for Infectious Diseases "L. Spallanzani", Via Portuense 292, 00149 Rome, Italy, +390655170277, Fax +390655170430

We write in relation to the editorial commentary from Khan et Tselis (1) who rightly suggest caution to consider chronic cerebrospinal venous insufficiency (CCSVI) as a pathological entity and cast serious doubt on its relevance to multiple sclerosis (MS); they forecast properly designed studies to investigate the relevance of CCSVI to MS, in order to carry out interventional procedures.

The absence of extracranial venous stenosis at the earliest stage of MS makes it an unlikely cause of the disease (2). The idea of venous congestion as a possible contributor to the pathogenesis of MS has been discussed for the past 40 years, but remained widely unappreciated by the scientific community.

In contrast with other authors, Zamboni et al (3) defined CCSVI as a vascular condition associated with MS; it is characterized by multiple intraluminal stenosing malformations of the principal pathways of extracranial venous drainage, particularly in the internal jugular veins (IJVs) and the azygous vein (AZY), that restrict the normal outflow of blood from the brain. In the study of Zamboni et al there was significant extracranial venous stenosis localised at the principal level of the cerebrospinal venous segments as detected by selective venography and anomalies of venous outflow at color Doppler high resolution examination. The pathological consequences of CCSVI have been hypothesised to emanate from chronic venous reflux and hypertension leading to increased iron deposition in the brain and subsequent MS pathology, including inflammation and neurodegeneration.

Other recent reports found no differences in cerebrospinal venous drainage using transcranial and extracranial Doppler imaging (4-5). The discrepancies in the results may be explained with the absence of standardized internationally accepted criteria for normal Doppler venous flow parameters (2).

We performed complete post-mortem examination of two patients with MS, died for different causes. One patient, a 74 year-old-woman, was hospitalized for acute respiratory illness and died because of bacterial pneumonia; the other one, a 35 year-old-woman, died for otogenic bacterial meningitis complicated with internal jugular thrombosis as demonstrated on MR venography.

Postmortem examination demonstrated in both patients a marked stenosis of left internal jugular vein at the apex of the angle formed by the two heads of the sternocleidomastoid muscle where the IJV overlie the carotid artery with ectasia and congestion of the intracranial veins. Venous flow slowing, caused by the stenosis, had predisposed to IJV thrombosis, histologically demonstrated in the second case.

Severe inflammatory disease may be a risk factor for deep venous thrombosis but also chronic cerebrospinal venous insufficiency. We demonstrate, for the first time as far as we are aware, the presence of anatomical alteration in the veins of the neck with impaired venous drainage from the central nervous system in two patients with multiple sclerosis who died from other causes.

We do not know the exact implications in MS pathology and certainly there is no doubt that this area warrants a great deal more study. Clinical trials for evaluating new therapeutic agents and other clinical experimental protocols may be required.

References: 1. Khan O, Tselis A. Chronic cerebrospinal venous insufficiency and multiple sclerosis: science or science fiction? J Neurol Neurosurg Psychiatry 2011;82:355. 2. Yamout B, Herlopian A, Issa Z Extracranial venous stenosis is an unlikely cause of multiple sclerosis Mult Scler 2010 16: 1341-9 3. Zamboni P, Galeotti R, Menegatti E, et al Chronic cerebrospinal venous insuffiency in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry 2009;80:392-9. 4. Doepp F, Paul F, Valdueza JM, et al No cerebrocervical venous congestion in patients with multiple sclerosis. Ann Neurol 2010, 68:173-183. 5. Sundstrom P, Wahlin A, Ambarki K, et al Venous and cerebrospinal fluid flow in multiple sclerosis: a case-control study. Ann Neurol 2010, 68:255-259.

Conflict of Interest: None declared

Published 28 April 2011