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Introduction
Aconcussion is a clinical condition characterized by the alteration of brain function involving loss of consciousness caused by the biomechanical forces affecting orientation and memory. It is often called a “mild form of traumatic brain injury” [1]. The word “concussion” is rooted in the Latin word “concussus,” which means shaking vigorously [2]. Approximately 3.8 million concussions are reported annually, with more than 50% participating in sports. The World Health Organization (WHO) has defined postconcussion syndrome as a syndrome occurring after trauma to the head, usually sufficient enough to cause lack of consciousness, and several other symptoms, including fatigue, irritability, headache, insomnia, impairment of memory, and reduced tolerance to stress, emotional excitement, dizziness, and difficulty in concentration and performing mental tasks [3]. 
Simultaneous stretching of axons, increased permeability, and disruption of neuronal membranes leads to diffuse axonal injury, which forms the ultrastructural basis of concussion [4, 5, 6]. Biochemical changes include the abrupt and sudden release of glutamate, an excitatory neurotransmitter [7]. An excessive accumulation of extracellular potassium and intracellular calcium resulting from abnormal ion fluxes causes a massive excitation and depolarization of neurons, accompanied by catabolism of compensatory homeostatic ion pump-driven glucose to generate more adenosine triphosphate (ATP), the energy currency of the cell—the excitation and hyperglycolysis phenomenon last several minutes to a few hours [8, 9]. The excitation phase is associated with seizures [10], followed by a wave of neuron suppression known as spreading depression. The depression occurs because of decreased ATP production due to malfunctioning of oxidation metabolism in the mitochondria, leading to early loss of consciousness, confusion, or amnesia found in concussed individuals [4, 6]. Cognitive deficits occur following a concussive injury due to dysfunctional neurotransmission in the cholinergic, adrenergic, or glutamatergic systems [6]. An abnormal elevation of intracellular calcium is part of a neurometabolic cascade of a concussion that occurs with the combined result of neuronal cell injury, including swelling of axons and disruption/cell deaths via apoptotic pathways [4, 6]. 
The manual therapy procedures used to treat postconcussion syndrome include neural manipulation, craniosacral therapy, and visceral manipulation. Upledger craniosacral therapy (CST) is a non-invasive type of manual therapy that includes gentle movements helping in the modification and correction of obstructions in the craniosacral system (CSS): Meninges, cerebrospinal fluid (CSF), CSS glia, and bones attached to the meninges. The craniosacral system surrounds the spinal cord and brain and protects, nourishes, and detoxifies the brain and spinal cord. Craniosacral therapy encourages the flow of cerebrospinal fluid into and out of the central nervous system (CNS) [11]. Autonomic nervous system (ANS) interactions and sensory and motor signals can be adversely affected if there are restrictions in the craniosacral system and its components, resulting in changes in the normal physiological processes of the brain and spinal cord [12]. Glial cells help maintain brain homeostasis, regulate blood circulation, regulate CSF production and flow, regulate neuronal signaling, and develop CNS [12, 13]. Barral visceral manipulation (VM) is a manual therapy technique with gentle and specifically placed manual forces that help encourage vascularity, tone, pressure, and normal mobility [14]. Barral neural manipulation (NM) is a manual therapy technique that removes the local nerve restrictions to restore and balance the pressure between the cranium [15]. These manual therapies (CST/VM/NM) treat the vascular, neurological, and structural tissues corresponding to the concussion injury [16]. 
Other manual therapy techniques for postconcussion syndrome management include lymphatic drainage, massage therapy, and osteopathic manipulative treatment. Lymphatic drainage is the manual therapy technique in which fluid evacuation uses specific rhythms like the Chikly method (light touch and brain curriculum). This technique activates lymphangions, the pumping unit of lymph vessels, which enhances fluid exchange. Lymphatic drainage influences the physiological systems of the whole body mechanically [17, 18]. Massage therapy is a manual technique that manipulates soft tissues for psychological and physiological benefits. Concussion symptoms can be managed by massage therapy [19]. Osteopathic manipulative treatment (OMT) is the manual therapy technique in which there is glymphatic flow facilitation with the help of muscle energy, myofascial release, and low amplitude, high velocity. This treatment aids in clearing the inflammatory molecules from the brain and improving oxygenation [20]. Concussion symptoms like vertigo and imbalance can be treated with OMT [21, 22]. It can also be accompanied by headaches compared to relaxation exercises alone [23].
There are many treatments for postconcussion syndrome, including physiotherapy, massage therapy, chiropractic adjustments, neuromuscular rehabilitation, soft laser therapy, craniosacral therapy, low-level laser therapy, cognitive rehabilitation, biofeedback/neurofeedback, and soft tissue treatment. As a result, there is enormous conflict among the existing treatment of postconcussion syndrome symptoms. Other approaches were pharmacotherapy and cognitive behavioral therapy provided by various health professionals. Physiotherapists, psychologists, and medical professionals (sports medicine physicians) offer treatment parameters for postconcussion symptoms recovery in postconcussion survivors [24]. The role of pharmacotherapy, vestibular physical therapy, cognitive rehabilitation, cognitive-behavioral therapy, education, rehabilitation programs, mindfulness-based interventions and relaxations, and rest has been well established, with many studies in the form of systematic reviews and even meta-analyses. There are numerous studies on novel postconcussion syndrome treatments, including hyperbaric oxygen therapy, exercise, and repetitive transcranial magnetic stimulation, in the form of systematic reviews and meta-analyses of the studies with and without randomization [25]. Manual therapies have been a topic of interest for many researchers and systematic reviewers who evaluated the effect of manual therapies on mechanical neck disorders [26] and migraines [27]. Thus, there is a shortage of research on manual therapy techniques’ influence on postconcussion syndrome recovery. So, this systematic review aims at determining the impact of manual therapies like massage therapy, craniosacral therapy, lymphatic drainage, visceral manipulation, neural manipulation, and osteopathic manipulative treatment in managing postconcussion syndrome-affected individuals in sports-related injuries, combating, mild traumatic brain injuries, and accidents. The variables for assessing the recovery of postconcussion syndrome symptoms include cervicogenic headache, anxiety, quality of life (QoL), cervical range of motion, cervical muscle strength, and sleep patterns. This systematic review will also help identify the best manual treatment technique amongst the existing ones.

Materials and Methods
Protocol and registration
The guidelines of PRISMA (the preferred reporting item for systematic reviews and meta-analyses) 2015 were utilized in this systematic review of nonrandomized studies [28]. 

Inclusion criteria
This systematic review will include only those studies that included: a) Participants diagnosed with postconcussion syndrome symptoms like immobility, balance issues, cervicogenic pain, altered quality of life, sleep disorders, and altered cognition irrespective of the mechanism of concussion injury; b) Participants of the adult population; c) Description of the outcomes of manual therapies intervention only; d) Measuring parameters of postconcussion syndrome symptoms recovery; e) Published in the English language with available full-text.

Exclusion criteria
This systematic review will exclude those studies which are: a) Unpublished research studies and conferences; b) Studies that combined manual therapies with other treatment techniques like exercise therapy, rest, or medications.

Information sources
A systematically comprehensive electronic search was performed on the databases, namely PubMed, Research Gate, and Google Scholar, within 10 years, from 2011 to 2021. An individual search was performed in these databases. Additional studies were done via manual search.

Search strategy
The search strategy included an initial search using key terms of “manual therapy,” “postconcussion syndrome,” “craniosacral therapy,” and “visceral manipulation.” These initial search terms were included in any combination. In the final search, ‘OR’ and ‘AND’ were used as Boolean operators in the form of “postconcussion syndrome and manual therapy,” which identified 5489 potential records. They included 10 articles from PubMed, 79 from Research Gate, and 5400 from Google Scholar. The manual search retrieved 4 articles during the process of identification. Following an initial screening of abstracts and titles, 317 records were selected in the screening process. During the screening phase, duplicates were removed in the Mendeley software, which provided 296 records. They were assessed based on the inclusion criteria, which provided 161 articles eligible for subsequent screening. From these, 119 were excluded as their full text was unavailable. Consequently, 42 articles were deemed fit for the procedure of eligibility assessment in which 35 full-text articles were excluded because 28 articles were found irrelevant, 5 studies were not in the English language, 1 was a review, and 1 dissertation. Finally, 7 articles remained and were included in the qualitative synthesis.

Study selection
Case series, case reports, and pilot studies were utilized in this systematic review because of the scarcity of research work (randomized clinical trials or randomized cross-over trials) in manual therapy interventions for postconcussion syndrome symptoms management. Reviews, overviews, meta-analyses, systematic reviews, dissertations, editorials, unpublished articles, letters, and pre-prints were excluded. Mendeley reference manager software was used to remove duplicates of electronic databases. The titles and abstracts of the identified records were screened, followed by full-text screening.

Data extraction and quality assessment
Data were extracted based on the study objectives. The primary outcome measures were different types of manual therapies for postconcussion syndrome management. The quality assessment of each study was done using the GRADE approach (grades of recommendation, assessment, development, and evaluation). The GRADE approach has 4 initial quality categories: High, moderate, low, and very low. Based on the GRADE approach, the case reports were graded very low, and case series and pilot studies were initially graded in the low category. Further potential grade changes are evaluated based on the five GRADE key factors. Five GRADE parameters were indirectness, publication bias, risk of bias, inconsistency, and imprecision [29].

Data collection process
The inclusion and exclusion criteria were applied to the studies retrieved from the search, irrespective of the methodological quality. Due to the unavailability of randomized studies, nonrandomized studies like case series, case reports, and pilot studies were included. However, meta-analysis, systematic reviews, unpublished work, and pre-prints were excluded. With the remaining pool of evidence, the GRADE approach was utilized. Final grade synthesis was done, and a group judgment was made with the approval of all review team members. A variety of study designs GRADE approach deemed fit for the quality appraisal for such nonrandomized studies [33].

Results
Study selection
A total of 317 potential articles were extracted from the database search via electronic media. Undergoing the PRISMA screening and eligibility procedure, only 7 articles were included in the qualitative synthesis [16, 19, 30, 31, 32, 33] The details of the study selection are shown in Figure 1. Out of 7 articles, there were 2 case series [16, 33], 4 case studies/reports [19, 20, 31, 32], and only 1 pilot study [30].

Study characteristics
Table 1 summarizes the characteristics of the studies included in this systematic review.

Participant’s characteristics of the studies included
Of 7 studies, 4 included athletic participants [16, 19, 31, 33], and the remaining 3 included non-athletic people [20, 30, 32]. The total number of participants included in the study was 32, of which 28 were males and 4 were females, from varied age groups ranging from 20 to 70 years.

Outcome measures used in included studies
Short form-36, also known as the SF-36 QoL survey, was utilized in 2 studies [16, 30]. One study used the postconcussion symptoms checklist outcome [31]. balance error scoring system (BESS) was used in 2 studies [19, 33]. Headache Impact-6 outcomes were used in 1 study [31]. Visual analog scale/numeric rating scale was utilized in 3 studies [16, 32, 33].

Quality assessment
The GRADE approach was used to assess the quality of included studies. The studies included in this systematic review were assessed based on their publication bias, risk of bias, indirectness, imprecision, and inconsistency. The 4 grades for reviewing the body of evidence of the study were high, moderate, low, and very low. Table 2 summarizes the quality of the included studies. The reviewers rated 4 studies [19, 20, 31, 32] in the very low category and 3 studies [16, 30, 33] in the low category, depending upon the study design.

Additional analysis
Effect of manual therapies on pain
Ten sessions of neural manipulation, visceral manipulation, and craniosacral therapy were administered in one series on 11 male retired professional football players diagnosed with postconcussion syndrome. They reported a statistically significant reduction in pain intensity, as illustrated through a numeric pain scale (P=0.0448) [16]. Another pilot study employed mixed light touch manual therapies, including craniosacral therapy, visceral manipulation, and brain curriculum in two sessions of 2 hours each on 10 participants with postconcussion symptoms from injury to the head and post-traumatic stress disorder. They reported a significant decrease in the pain level (P=0.039) [30]. A case series on 7 patients with sports-related concussions used cervical, vestibulo-ocular, and manual therapy rehabilitation and reported a change in the pain level on the numeric rating scale (mean=4.3) [33]. A case study was performed in which massage therapy was administered as concussion treatment and found significant changes in pain levels on the visual analog scale—before the treatment, it was 8-9/10. After treatment, it was 0/10 [19].

Effect of manual therapies on headache
A significant decrease in headache (P=0.031) was reported in the pilot study of 10 patients on applying mixed light touch manual therapies (LTMT) protocols of two sessions of 2 hours each. Measure yourself medical outcome profile-2 was utilized to measure headache intensity [30]. A case study was done on a 24-year-old athlete with postconcussion syndrome symptoms and reported 90% relief from the initial headache level on the headache impact test-6 outcomes till the eleventh session. The researcher used specific craniosacral therapy techniques and manual lymphatic drainage techniques [31]. In a case study, craniosacral therapy was implemented in a patient with a traumatic brain injury that reported decreased headache intensity on a 10 cm visual analogue scale from 6-9 cm to 2-4 cm in the weeks intervention [32]. A case study on massage techniques for concussion treatment reported significant positive outcomes on headache intensity [19].

Effect of manual therapies on cervical range of motion 
A case series was performed on 11 individuals diagnosed with postconcussion syndrome [16]. The cervical range of motion was reported to increase with the manual therapy interventions with a statistically significant (P=0.0377). Another case study was conducted utilizing massage therapy techniques like soft tissue release and reported significant changes in the range of motion of the cervical spine. Before the intervention, there was reduced cervical rotation, lateral tilt, and forward flexion, while after the treatment, the cervical spine range of motion was within the normal range in all planes based on muscle testing of the cervical spine [19].

Effect of manual therapies on balance
A case study on concussion treatment utilizing massage techniques was conducted, which reported a significant change in the BESS (balance error scoring system) from 60/60 to 35/60 [19]. Another study was a case series of symptomatic treatment for sports-related concussion rehabilitation in adolescents. An average decrease of 17.4/60 in BESS scores was reported (the minimum detectable change was 9.3) [33]. A case report was conducted to resolve concussion symptoms after osteopathic manipulation, which reported an increase in the equilibrium from 76 pre-treatment to 81 post-treatment on the sensory organization test on SMART balance master [20].

Effect of manual therapies on sleep
Sleep disturbance was founded to decrease (P=0.508) on the neuro-QoL SF v 1.0 survey. In this study, a pilot study of 10 participants was performed in treatment [30]. Similarly, average hours of sleep per night were reported to increase on 5 days of treatment and continued to increase until follow-up in the case series [16].

Effect of manual therapies on QoL
In a case series performed on 11 retired male professional football players, QoL was significantly increased on the follow-up concerning energy level, general health, social functioning, and emotional wellbeing and social functioning, using the short form-36 survey-QoL survey [16]. A pilot study evaluating the influence of mixed LTMT on chronic post-traumatic stress disorder and injury to the head among duty soldiers reported that LTMT had improved the QoL with respect to positive effects and wellbeing in social roles and activities. There is no change in the applied cognition executive functions, sleep disturbance, and satisfaction with QoL’s social roles and activities parameters. There is a negative effect of LTMT on QoL factors like emotional and behavioral dysfunction, upper and lower extremity mobility, applied cognition, stigma, and general concerns. The neuro-QoL bank v1.0 was utilized for reporting the respective increase and decrease in QoL parameters [30].

Discussion
This systematic review was performed to determine the impact of manual therapies on postconcussion syndrome symptoms recovery parameters. After the systematic search, 7 articles were found, with study design levels ranging from very low to low quality because their design was case series and case report [16, 30, 33]. The remaining 4 studies were rated as very low quality consisting of a case report/study as a study design [19, 20, 31, 32]. Further research should support this evidence. 
Regarding the study design, the highest quality of manual therapy interventions was seen in the pain reduction of the postconcussion syndrome [16, 19, 30, 33].However, manual therapies play a significant role in the resolution of several other postconcussion symptoms as reported in low-quality evidence like reduction in headache intensity [19, 20, 31, 32], improvement in balance [19, 20, 33], improvement in QoL [16, 30], increased cervical range of motion [16, 19] and improvement in sleep patterns [16, 30]. Several other parameters of postconcussion symptoms recovery were insignificant in applying manual therapies, like cognition, immobility, memory, and reaction time. According to the synthesis of evidence, it is indicated that individuals with postconcussion syndrome may get benefited from manual therapy techniques. Manual techniques like craniosacral, massage, visceral, and neural manipulation may reduce postconcussion symptoms like pain, balance, quality of life, and headache. 
In this systematic review, 7 studies examined manual therapy in postconcussion syndrome recovery. Different types of manual therapeutic techniques were utilized, which are craniosacral therapy [16, 30, 31, 32], massage therapy [19], visceral manipulation [16, 30], manual lymphatic drainage [31], neural manipulation [16], brain curriculum [30], osteopathic manipulative treatment [20], and generalized manual therapy (soft tissue mobilizations; thoracic manipulation and spinal mobilization) [33].
The results of this systematic review revealed that out of 6 manual therapy techniques for concussion management (craniosacral therapy, visceral manipulation, neural mobilization, massage therapy, osteopathic manipulative treatment, and general manual therapy), the most effective treatment was craniosacral therapy which was used in 4 studies [16, 30, 31, 32], followed by the visceral manipulation in two studies [16, 30]. Little evidence was in favor of the osteopathic manipulative treatment [20], massage therapy [19], brain curriculum [30], general manual therapy [33], and neural manipulation [16]. Thus, different types of manual therapies were incorporated in the included studies as a treatment intervention revealing a varied range of effects on the different parameters of the postconcussion syndrome symptoms recovery.

Study limitations
This systematic review had several limitations because the included studies have low quality, initially leading to uncertainty in making more robust conclusions. The limitations included a small sample size, lower-level study designs, and inconsistency in sample inclusion criteria (e.g. athletic and non-athletic population). Different tests and outcome measures were utilized in the included studies to perform the data analysis. These factors contribute to difficulty in synthesizing results across the included studies. One study by Davis et al. [30] included patients with post-traumatic stress disorder for prolonged periods and head injury. Likewise, in another case study by Haller et al. [32], the inclusion criterion was whether the postconcussion syndrome symptoms recovered. Thus, further research is required to provide clarification in the form of strong evidence studies like randomized controlled trials and cross-over trials. Studies included in this review had different protocols and methodologies. Some studies have conducted follow-ups [16, 30, 31, 32], while the remaining studies have not [19, 20, 32]. There is variation in the timing of intervention of the included studies. A 25-min single session of osteopathic manipulative treatment was given in one study [20], while in another study, there was a complete 2-week inpatient treatment [32]. In another study, two 45-min sessions with 2 days rest in between was conducted [19]. On the other hand, a 3-phased treatment plan including cervical, vestibulo-ocular, and manual therapy components was executed in one study [33]. Similarly, one study gave treatment for 5 days twice per day, and another pilot study in which two sessions of 60 minutes duration were scheduled 1 week apart [30]. Hence, the variation in the treatment duration exists in the studies included.
Also, there was limited access to the database making the review dependent on open-access databases like PubMed, Google Scholar, and Research Gate. Search algorithms were limited, too. Another limitation lies in the lack of generalized findings of the results of the included studies.

Future scope of the study
Postconcussion syndrome is a major concern as it may cause serious illnesses in the athletic and non-athletic populations. Physical therapists specializing in sports and neurological conditions can find this systematic review valuable in gaining knowledge regarding the new treatment in postconcussion recovery. The present study seems to be the first systematic review evaluating the existing contribution of manual therapeutics in treating individuals diagnosed with postconcussion syndrome. There is a growing requirement for the firm–quality evidence regarding postconcussion interventions to determine the beneficial effects of manual therapy and enable physiotherapists and manual therapy practitioners to include these treatment options to rehabilitate postconcussion syndrome patients. There is a shortage or lack of research evaluating manual therapy intervention in these populations. This systematic review is going to provide preliminary evidence for future studies. This study revealed different intensities of the effect of manual therapies on various parameters of postconcussion syndrome symptoms recovery. Of the 7 eligible studies, 4 claimed the effectiveness of manual therapies on the pain parameter and headache parameter of the postconcussion syndrome symptoms recovery, respectively. Three studies demonstrated the effectiveness of manual therapies on balance, and 2 studies showed efficacy on QoL, cervical range of motion, and sleep. Several other parameters, like dizziness, sleep disorders, and cognition, seem unaffected. Craniosacral therapy was most effective compared to other manual therapy techniques. This review further highlights the need for future good-quality randomized studies to support and confirm the existing findings and gather fruitful information regarding the effectiveness of manual therapy techniques in postconcussion syndrome. Upcoming research can focus on clinical trials, cohort studies, and cross-over trials so that meta-analysis can be performed and high-quality evidence can be gathered.

Conclusion
The results of this systematic review conclude that manual therapies are a treatment option for managing an individual diagnosed with postconcussion syndrome. Craniosacral therapy was the manual therapy technique that was found most effective in managing individuals with postconcussion syndrome. However, more studies were required in randomized controlled and clinical trials to reach any firm conclusion.

Ethical Considerations
Compliance with ethical guidelines
The protocol of this systematic review was registered by PROSPERO (Code: CRD42021239078).

Funding
This research did not receive any grant from funding agencies in the public, commercial, or non-profit sectors.

Authors' contributions
All authors equally conducted this systematic review.

Conflict of interest
The authors declared no conflict of interest.

Acknowledgments
Sincere gratitude to the faculty members of Student Research Committee, Department of Physiotherapy, Faculty of Allied Health Sciences, Manav Rachna International Institute of Research and Studies, who helped in conduct of this systematic review.


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