Beneficial effects of autologous mesenchymal stem cell transplantation in active progressive multiple sclerosis.

In this study (trial registration: NCT02166021), we aimed to evaluate the optimal way of administration, the safety and the clinical efficacy of mesenchymal stem cell (MSC) transplantation in patients with active and progressive multiple sclerosis. Forty-eight patients (28 males and 20 females) with progressive multiple sclerosis (Expanded Disability Status Scale: 3.0-6.5, mean : 5.6 ± 0.8, mean age: 47.5 ± 12.3) and evidence of either clinical worsening or activity during the previous year, were enrolled (between 2015 and 2018). Patients were randomized into three groups and treated intrathecally (IT) or intravenously (IV) with autologous MSCs (1 × 106/kg) or sham injections. After 6 months, half of the patients from the MSC-IT and MSC-IV groups were retreated with MSCs, and the other half with sham injections. Patients initially assigned to sham treatment were divided into two subgroups and treated with either MSC-IT or MSC-IV. The study duration was 14 months. No serious treatment-related safety issues were detected. Significantly fewer patients experienced treatment failure in the MSC-IT and MSC-IV groups compared with those in the sham-treated group (6.7%, 9.7%, and 41.9%, respectively, P = 0.0003 and P = 0.0008). During the 1-year follow-up, 58.6% and 40.6% of patients treated with MSC-IT and MSC-IV, respectively, exhibited no evidence of disease activity compared with 9.7% in the sham-treated group (P < 0.0001 and P < 0.0048, respectively). MSC-IT transplantation induced additional benefits on the relapse rate, on the monthly changes of the T2 lesion load on MRI, and on the timed 25-foot walking test, 9-hole peg test, optical coherence tomography, functional MRI and cognitive tests. Treatment with MSCs was well-tolerated in progressive multiple sclerosis and induced short-term beneficial effects regarding the primary end points, especially in the patients with active disease. The intrathecal administration was more efficacious than the intravenous in several parameters of the disease. A phase III trial is warranted to confirm these findings.

Use of DWI-only MR protocol for screening stroke mimics.

PURPOSE: Patients presenting with focal neurological symptoms may suffer from stroke or stroke mimics. Diffusion weighted MRI (DWI) is highly sensitive for identifying acute ischemia. Therefore, we aimed to explore whether a DWI-only protocol would help differentiate stroke from stroke mimics. METHODS: We identified all patients with possible but not definite stroke that underwent DWI-only MRI between 6/2010 and 8/2011. Patients with a positive DWI lesion were compared to those with negative DWI findings on demographics, risk factor profile, final discharge diagnoses, and outcome. RESULTS: A total of 124 patients were included with a median age of 63.5 (53% male). DWI MRI was positive for acute ischemia in 46 patients (37%). The most frequent stroke mimics were peripheral vertigo (n=19), acute confusion (n=10), seizures (n=9) and migraine with aura (n=8). Most ischemic lesions were small on DWI (<2 cm) and patients had minor disability (mean NIHSS 4.9±3.9) with 81% of patients having good outcomes (modified Rankin Score≤2) at 3 months. On univariate analysis patients with positive DWI studies had higher frequencies of having more than one clinical symptom (56% vs. 13% respectively; P<0.001) and this variable remained a significant predictor for stroke on multivariate analysis (OR 9.4 95% CI 3.8-23.5). CONCLUSIONS: A short DWI-only MRI protocol can effectively differentiate stroke from stroke mimics and could be used in settings of the emergency department as well as later on for diagnostic purposes. The chances for finding positive DWI lesions are increased in patients with multiple symptoms and signs.

Incidence of DWI-positive stroke in patients with vertigo of unclear etiology, preliminary results.

BACKGROUND: Acute vertigo may be secondary to stroke or to non-ischemic causes. Accurate identification of vertigo secondary to ischemia may lead to appropriate timely intervention that can minimize stroke-related damage and can help in tailoring the most appropriate individual therapy for affected patients. Diffusion weighted MRI (DWI) is very accurate for diagnosing stroke and we therefore aimed to test whether it can aid in making a correct diagnosis of vertigo secondary to stroke. METHODS: All patients presenting with vertigo in which the diagnosis of stroke was considered underwent DWI only MRI. Data regarding the symptoms and neurological deficits, vascular risk factors, imaging findings, and outcomes was accrued. Patients with stroke on DWI were compared with those without ischemia. RESULTS: Between June 2010 and August 2011, 28 patients fulfilling the entry criteria were identified with a mean age of 62·2±12·8 (60% male). The final diagnosis was stroke in 11 patients (39%). Patients with stroke did not differ from those without stroke in their risk factor profile. However, patients with stroke more often tended to present with vertigo accompanied by other neurological symptoms (73% versus 12% respectively, P = 0·001). After adjusting for age and the presence of diabetes, the presence of multiple symptoms remained the only variable that was associated with a positive DWI scan (odds ratio: 30: 95% confidence interval: 2·6-349). Most patients with stroke had very mild strokes with a median admission NIHSS score of 3 and DWI lesion volumes >2 cm were found in only three patients. Most stroke patients made a good recovery (modified Rankin score ≤2 in seven of nine patients with 90 day data). The most common diagnosis in patients without stroke was of vertigo of peripheral origin (14/17). CONCLUSIONS: DWI only MRI can be used to rapidly screen patients presenting with vertigo and suspected vertebrobasilar stroke. The occurrence of vertigo in combination with other focal neurological symptoms may increase the accuracy of stroke diagnosis but is not sensitive or specific enough. Combining clinical presentation patterns with DWI data may enable rapid decision making as to treatment options.

An animal model for assessment of heat distribution and neural damage around the endo shears coagulation device-applications for laparoscopic nerve-sparing surgery.

BACKGROUND AND PURPOSE: Current urologic laparoscopic procedures include preservation of locoregional nerve fibers. The use of electrical coagulation is limited because of tissue conductance of current and heat production. While ultrasonic coagulation does not use electricity, heat is still produced. We designed an animal model to characterize the heat spread around ultrasonic devices and assess whether it is neurodestructive. MATERIALS AND METHODS: 10 rats were anesthetized; their skin was reflected, exposing the muscles. An ultrasonic probe was introduced into the tissue, and coagulation was performed for 10 seconds. Tissue temperature was measured using four thermocouples, at distances of 4, 8, 12, and 16 mm from the probes and in a circumferential manner. Thermal mapping of the probes was performed with an infrared camera. Further, four rats were anesthetized; the skin above their inner thighs was reflected bilaterally exposing the "nervus ischiadicus." Coagulation was performed in varying distances from the nerve on one side while the other served as control. One week later, the animals were sacrificed, and the nerves were obtained. Silver staining was used to assess the vitality of the axons. RESULTS: In distances of 4 to 8 mm from the device, temperatures as high as 81°C were recorded, and silver staining showed severe axonal damage. CONCLUSIONS: Although ultrasonic coagulation is efficient, local heat production may reach neurodestructive levels with a typical tissue distribution pattern. These features should be addressed during laparoscopic dissection and when considering nerve-sparing procedures.

Neurotropism of herpes simplex virus type 1 in brain organ cultures.

The mechanism of herpes simplex virus type 1 (HSV-1) penetration into the brain and its predilection to infect certain neuronal regions is unknown. In order to study HSV-1 neurotropism, an ex vivo system of mice organotypic brain slices was established and the tissue was infected with HSV-1 vectors. Neonate tissues showed restricted infection confined to leptomeningeal, periventricular and cortical brain regions. The hippocampus was the primary parenchymatous structure that was also infected. Infection was localized to early progenitor and ependymal cells. Increasing viral inoculum increased the intensity and enlarged the infected territory, but the distinctive pattern of infection was maintained and differed from that observed with adenovirus and Vaccinia virus. Neonate brain tissues were much more permissive for HSV-1 infection than adult mouse brain tissues. Taken together, these results indicate a complex interaction of HSV-1 with different brain-cell types and provide a useful vehicle to elucidate the mechanisms of viral neurotropism.