Manifestations and impact of the COVID-19 pandemic in neuroinflammatory diseases.

OBJECTIVE: To report initial results of a planned multicenter year-long prospective study examining the risk and impact of COVID-19 among persons with neuroinflammatory disorders (NID), particularly multiple sclerosis (MS). METHODS: In April 2020, we deployed online questionnaires to individuals in their home environment to assess the prevalence and potential risk factors of suspected COVID-19 in persons with NID (PwNID) and change in their neurological care. RESULTS: Our cohort included 1115 participants (630 NID, 98% MS; 485 reference) as of 30 April 2020. 202 (18%) participants, residing in areas with high COVID-19 case prevalence, met the April 2020 CDC symptom criteria for suspected COVID-19, but only 4% of all participants received testing given testing shortages. Among all participants, those with suspected COVID-19 were younger, more racially diverse, and reported more depression and liver disease. PwNID had the same rate of suspected COVID-19 as the reference group. Early changes in disease management included telemedicine visits in 21% and treatment changes in 9% of PwNID. After adjusting for potential confounders, increasing neurological disability was associated with a greater likelihood of suspected COVID-19 (ORadj  = 1.45, 1.17-1.84). INTERPRETATIONS: Our study of real-time, patient-reported experience during the COVID-19 pandemic complements physician-reported MS case registries which capture an excess of severe cases. Overall, PwNID seem to have a risk of suspected COVID-19 similar to the reference population.

Hydration status substantially affects chronic cerebrospinal venous insufficiency assessments.

We sought to determine the effect of hydration on the criteria for chronic cerebrospinal venous insufficiency (CCSVI), a proposed hypothesis for the etiology of multiple sclerosis (MS). Sixteen subjects (11 MS and 5 controls) were asked to fast overnight. The following morning, 2 CCSVI ultrasound examinations were performed: 1 in the mildly dehydrated state, and another 30-45 minutes after rehydrating with 1.5 L of Gatorade. Seven subjects fulfilled CCSVI criteria in the dehydrated state. Of these, 5 (71%) no longer fulfilled CCSVI criteria after rehydration. One additional subject met CCSVI criteria only after rehydration. Hydration status has a substantial effect on CCSVI criteria, suggesting that the sonographic findings of CCSVI may represent a physiologic rather than pathologic state.

A technical approach to dissecting and assessing cadaveric veins pertinent to chronic cerebrospinal venous insufficiency in multiple sclerosis.

OBJECTIVE: To establish a detailed technical procedure for studying the anatomical correlates of chronic cerebrospinal venous insufficiency in cadavers of multiple sclerosis and control subjects, and to present our findings of the normal anatomic venous structures, with reference to previous descriptions from the literature. METHODS: This study examined the internal jugular veins (IJVs), the brachiocephalic veins, and the azygos vein from 20 cadavers (10 control and 10 multiple sclerosis). These veins were exposed, isolated by clamps from the rest of the venous system, flushed with water, and then injected with fluid silicone from the superior ends of both IJVs. After the silicone cured to its solid state, the venous tree was removed en bloc and dissected longitudinally to expose the luminal surface. All vein segments were analyzed for anatomic variation. Anatomical analysis for this manuscript focused on normal vein architecture and its variants. RESULTS: Thirty-seven of 40 IJVs contained valves: 29 bicuspid, 6 tricuspid, and 2 unicuspid. The average circumferences of the right and left IJVs were 2·2 and 1·8 cm, respectively. Thirteen of 20 azygos veins contained a valve, located on average 3·6 cm away from the superior vena cava junction. Nine of the 13 azygos valves were bicuspid; four were tricuspid. Only one of the 40 brachiocephalic veins contained a valve. DISCUSSION: We detailed a technical approach for harvesting cadaveric neck and thoracic veins with relevance to chronic cerebrospinal venous insufficiency. The anatomy of the venous system has significant variability, including differing number of valves in different regions and variable characteristics of the valves. Average vein circumference was less than that typically reported in imaging studies of live patients.

Chronic cerebrospinal venous insufficiency as a cause of multiple sclerosis: controversy and reality.

OPINION STATEMENT: Multiple sclerosis (MS) is a relapsing and progressive disorder of the central nervous system. It is characterized most commonly by episodes of clinical worsening, followed by clinical improvement. Pathologically, MS is associated with focal areas of myelin destruction, inflammation, and axonal transection ("demyelinating plaques") in the brain and spinal cord. Traditionally, MS has been considered an autoimmune disorder, with the primary pathophysiology arising from an errant immune system. Recent work has raised the possibility that MS is not caused primarily by an immune abnormality but may instead arise from venous anomalies affecting the jugular and/or azygos venous systems. This condition has been called chronic cerebrospinal venous insufficiency (CCSVI). It has been proposed that CCSVI may be pathogenic in MS, causing venous back pressure and iron deposition, with a secondary immune response. Some investigators have proceeded to unblinded nonrandomized angioplasty and stenting procedures in patients with CCSVI, with anecdotal reports of symptom improvement. Because of conflicting data on the presence of CCSVI and the absence of controlled trials of CCSVI intervention, the current standard of clinical care is neither to evaluate multiple sclerosis (MS) patients for CCSVI anomalies, nor to intervene with procedures to alter such anomalies. There is intense interest and ongoing work to evaluate the presence of venous anomalies in MS patients as well as in normal controls and patients with other neurologic conditions; to characterize such anomalies, if present; and to further understand whether the concept of a "backpressure" pathology is borne out by the evidence. If CCSVI is indeed a pathogenic mechanism for some subset of the MS population, this would dramatically change the focus of attention for therapeutic endeavors and monitoring for this population and would bring MS therapeutics firmly into the area of vascular intervention. On the other hand, the history of MS research contains many novel and potentially paradigm-shifting ideas that were later disproved by other investigators.