Clinical trial NCT05889169: Stroke-induced Immunodepression in Neurorehabilitation
Official title: Stroke-induced Immunodepression: Role in the Neurorehabilitation Setting
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Stroke
Lymphopenia
Immunosuppression
Keywords: Ischemic stroke
Intracerebral hemorrage
Neurological rehabilitation
Neurorehabilitation
Cerebrovascular disorders
Immunodepression
Lead sponsor: IRCCS National Neurological Institute "C. Mondino" Foundation
Sponsor class: OTHER
First posted: 2023-06-05
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Participants were selected from a single centre cohort admitted for stroke rehabilitation at the Neurorehabilitation Unit of the IRCCS Mondino Foundation (Pavia, Italy).

Brief summary: The close interconnection between nervous system and the immune system is well known. Brain injuries lead to homeostasis disruption. On the one hand they result in increased brain inflammation contributing to tissue repair, at the expense of a possible extension of tissue damage. On the other hand, they lead to systemic down-regulation of innate and adaptive immunity, determining higher vulnerability to infections, responsible of death and comorbidities in the acute and subacute setting.

Aim of the study was to evaluate the role of immunosuppression in the neurorehabilitation pathway in patients with stroke.

Detailed description: The perfect balance between nervous and immune system could be severely impaired after brain injuries, such as strokes.

In the acute phase, inflammatory mediators are responsible of central nervous system inflammation, associated to tissue repair at the expense of possible secondary brain injury or damage expansions.

In the mean time, activation of hypothalamic-pituitary-adrenal axis and the autonomic nervous system determine downregulation of innate and adaptive immunity, with decreased circulating T cell count and reduced lymphocytic response. The degree of these changes is linked to the severity of brain damage and inevitably lead to higher vulnerability to infections, representing a negative prognostic factor in the acute phase.

Association between immunosuppression and functional outcome in the neurorehabilitation setting are missing.

Aim of this study was to evaluate the role of immunosuppression in the neurorehabilitation journey in patients with stroke.

We analyzed the neutrophil-to-lymphocyte ratio, a useful tool to investigate alterations in both the innate and adaptive immune systems. We correlated it to clinical and neurorehabilitation scales, investigating disability, functional status, as well as gait analysis and occurrence of infectious complications. All outcomes were measured on admission in Neurorehabilitation setting and at hospital discharge.

Eligibility criteria: Inclusion Criteria:

* diagnosis of first episode of ischemic stroke or primary spontaneous intracerebral haemorrhage (both confirmed by proper neuroimaging)
* admission to the Neurorehabilitation ward within 30 days from the index event

Exclusion Criteria:

* medical history of immunodeficiency or immunoproliferative disease
* immunosuppressive or immunomodulating therapy in the year before the index event
* systemic steroids in the six months before the index event
* Glasgow Coma Scale \< 8 at hospital admission
* other diagnosis of neurological diseases
* missing clinical/demographic data

Primary outcomes:
measure: Difference between group 1 and group 2 in FIM score (Functional Independence Measure) after rehabilitation
timeFrame: After four to eight weeks from NRB admission
Secondary outcomes:
measure: Difference between group 1 and group 2 in NIHSS score (National Institutes of Health Stroke Scale) after rehabilitation
timeFrame: After four to eight weeks from NRB admission
measure: Difference between group 1 and group 2 in Barthel Index after rehabilitation
timeFrame: After four to eight weeks from NRB admission
measure: Difference between group 1 and group 2 in Tinetti score after rehabilitation
timeFrame: After four to eight weeks from NRB admission
measure: Difference between group 1 and group 2 in Hauser Ambulation Index score after rehabilitation
timeFrame: After four to eight weeks from NRB admission
measure: Difference between group 1 and group 2 in infectious complication during rehabilitation
timeFrame: After four to eight weeks from NRB admission
Other outcomes:
Locations:
city: Pavia
country: Italy
facility: Headache Science & Neurorehabilitation Center
Study officials:
References:
citation: Meisel C, Schwab JM, Prass K, Meisel A, Dirnagl U. Central nervous system injury-induced immune deficiency syndrome. Nat Rev Neurosci. 2005 Oct;6(10):775-86. doi: 10.1038/nrn1765.
citation: Shi K, Wood K, Shi FD, Wang X, Liu Q. Stroke-induced immunosuppression and poststroke infection. Stroke Vasc Neurol. 2018 Jan 12;3(1):34-41. doi: 10.1136/svn-2017-000123. eCollection 2018 Mar.
citation: Chamorro A, Meisel A, Planas AM, Urra X, van de Beek D, Veltkamp R. The immunology of acute stroke. Nat Rev Neurol. 2012 Jun 5;8(7):401-10. doi: 10.1038/nrneurol.2012.98.
citation: Morotti A, Marini S, Jessel MJ, Schwab K, Kourkoulis C, Ayres AM, Gurol ME, Viswanathan A, Greenberg SM, Anderson CD, Goldstein JN, Rosand J. Lymphopenia, Infectious Complications, and Outcome in Spontaneous Intracerebral Hemorrhage. Neurocrit Care. 2017 Apr;26(2):160-166. doi: 10.1007/s12028-016-0367-2.
citation: Wartenberg KE, Stoll A, Funk A, Meyer A, Schmidt JM, Berrouschot J. Infection after acute ischemic stroke: risk factors, biomarkers, and outcome. Stroke Res Treat. 2011;2011:830614. doi: 10.4061/2011/830614. Epub 2011 Jun 12.