Case Series on Neurological Rehabilitation in Patients with Relapsing-Remitting Multiple Sclerosis

Presentation: Four patients, all females between the ages of 59 and 68 years, presented to Plasticity Brain Centers of Orlando for evaluation and treatment of relapsing-remitting multiple sclerosis (RRMS). All patients reported numbness and tingling, and balance issues, as symptoms.

Findings: When asked to rate their numbness and tingling on a graded symptom checklist (GSC) (Simon 2017), on a scale of 0 to 6 (with 0 being none and 6 being very severe), the average intensity was calculated as 4.25. A Comprehensive Assessment of Postural Systems (CAPS®) (Pagnacco 2014) was performed assessing each patient's balance and stability, on both a solid and foamed surface, with their eyes opened, eyes closed, and with multiple head positions. Their average balance score on intake was calculated as 26.14975%.

Methods: A 5-day, multi-modal program of neurological exercises was administered in 10 one-hour treatment sessions (Carrick 2017). Each session consisted of repetitive peripheral somatosensory stimuli, neuromuscular reeducation exercises, vestibular rehabilitation exercises (Herbert 2011) (Ozgen 2015), orthoptic exercises, and off-vertical axis rotation (Gdowski 1999) utilizing a multi-axis rotational chair (MARC).

Outcome: Upon exit, average numbness and tingling ratings were calculated as 1 (-74.71%), with two patients reporting complete resolution (a score of 0) (-100.00%). Stability scores improved, with the average stability score calculated as 33.2065% (+ 28.1925%).

Conclusion: The authors suggest that multi-modal program of neurological exercise may be a viable intervention to address stability and paresthesia in patients with RRMS. The authors also suggest further investigation into multi-modal, intensive neurological approaches for patients with RRMS.

References:
Carrick FR, Clark JF, Pagnacco G, Antonucci MM, Hankir A, Zaman R and Oggero E (2017) Head–Eye Vestibular Motion Therapy Affects the Mental and Physical Health of Severe Chronic Postconcussion Patients. Front. Neurol. 8:414. doi: 10.3389/fneur.2017.00414
Gdowski GT, McCrea RA. Integration of vestibular and head movement signals in the vestibular nuclei during whole-body rotation. J Neurophysiol (1999) 82:436–49
Herbert JR, Corboy JR, Manago MM, Schenkman M. Effects of vestibular rehabilitation on multiple sclerosis related fatigue and upright postural control: a randomized controlled trial. Physical therapy (2011) Aug; 91(8): 1166-83. Doi: 10.2522/ptj.20100399. Epub 2011 Jun 16.
Ozgen G, Karapolat H, Akkoc Y, Yuceyar N. Is customized vestibular rehabilitation effective in patients with multiple sclerosis? A randomized controlled trial. European journal of physical and rehabilitation medicine (2016) Aug;52(4): 466-78. Epub 2016 Apr 6.
Pagnacco G, Carrick FR, Wright CH, Oggero E. In-situ verification of accuracy, percision and resolution of force and balance platforms. Biomed Sciences instrumentation (2014) 50:171-8
Simon M, Maerlender A, Metzger K, Decoster L, Hollingworth A, McLeod TV. Reliability and Concurrent Validity of Select C3 Logix Test Components. Developmental Neuropsychology (2017) Oct; 0: 1-14. Doi: 10.1080/87565641.2017.1383994. Epub 2017 Oct 25.
Keywords: Multiple Sclerosis, Vestibular Rehabilitation, Neurorehabilitation, Orthoptics, Physical Therapy Modalities, chiropractic neurology, balance, Paresthesia, posturography, non-invasive neuromodulation

Conference: International Symposium on Clinical Neuroscience 2018, Orlando, Florida, United States, 24 May - 26 May, 2018.

Presentation Type: Poster

Topic: Clinical Applications in health, disease, and injury to the nervous system

Citation: Kalambaheti ER, Manno MM and Antonucci MM (2018). Case Series on Neurological Rehabilitation in Patients with Relapsing-Remitting Multiple Sclerosis. Front. Neurol. Conference Abstract: International Symposium on Clinical Neuroscience 2018. doi: 10.3389/conf.fneur.2018.60.00004

Received: 22 Feb 2018; Published Online: 28 Mar 2018.

Correspondence: Dr. Emily R Kalambaheti, Plasticity Brain Centers, Orlando, FL, United States, Emily.Kalambaheti@gmail.com
Objective: The objective of this study is to test whether head–eye vestibular motion (HEVM) therapy is associated with decreased symptoms and increased function in postconcussive syndrome (PCS) patients that have been severely impaired for greater than 6 months after a mild traumatic brain injury.

Design: Retrospective clinical chart review.

Setting and participants: Tertiary Specialist Brain Rehabilitation Center.

Interventions: All subjects underwent comprehensive neurological examinations including measurement of eye and head movement. The seven modules of the C3 Logix Comprehensive Concussion Management System were used for pre- and postmeasurements of outcome of HEVM therapy.

Materials and methods: We utilized an objective validated measurement of physical and mental health characteristics of our patients before and after a 1-week HEVM rehabilitation program. We included only PCS patients that were disabled from work or school for a period of time exceeding 6 months after suffering a sports concussion. These subjects all were enrolled in a 5-day HEVM rehabilitation program at our Institutional Brain Center with pre- and post-C3 Logix testing outcomes.

Results: There were statistical and substantive significant decreases in PCS symptom severity after treatment and statistical and substantive significant increases in standardized assessment of concussion scores. The outcomes were associated with positive changes in mental and physical health issues. This is a retrospective review and no control group has been included in this study. These are major limitations with retrospective reviews and further investigations with prospective designs including a randomized controlled study are necessary to further our understanding.

Conclusion: Head-eye vestibular motion therapy of 5 days duration is associated with statistical and substantive significant decreases of symptom severity associated with chronic PCS.

Introduction
Traumatic brain injury (TBI) is caused by extracranial mechanical forces. These injuries may be associated with a loss of consciousness and memory impairment for recent events surrounding the head injury with changes of mental status at the time of the injury (1). Unfortunately, there is a lack of reliable and efficient evidence-based treatments for the approximately 1.8–3.6 million traumatic brain injuries that are reported annually in the United States (2) and we wanted to contribute to better clinical outcomes. Mild traumatic brain injury (mTBI), even in the chronic phase years postinjury, is not a benign condition but is associated with increased rates of headaches, sleep problems, and memory difficulties. Furthermore, mTBI can complicate or prolong recovery from preexisting or comorbid conditions such as post-traumatic stress disorder, a neuropsychiatric condition (3). Such patients may demonstrate difficulty with executive functionality and exhibit a mental inflexibility that may render them powerless to shift their focus between concepts (4).

Alarmingly, 20–30% of patients that suffer a mild closed head injury (mCHI) are affected by the incapacitating syndrome of a postconcussive syndrome (PCS) that complicates recovery and contributes to symptoms that may be considered to be neuropsychiatric in nature (5). In fact, mental health issues are related to a history of concussions resulting in possible severe and long-term influence on PCS patients, families, and friends (6).

The likelihood of depression and PCS increases after mTBI and is linked with reduced psychosocial outcomes including an increased probability of self-reported disability, underemployment, low income, and marital problems (7). Adolescents also may be depressed after suffering a concussion and should be screened for depression (8) due to the psychological sequelae that might impair their psychosocial functioning (9). We are concerned with the adverse long-term psychiatric, neurologic, and psychological morbidities that complicate recovery from PCS. mTBI patients that are depressed report increased mental health issues (10) that may confound diagnostic and therapeutic interventions that might be helpful. Many patients might describe only physical symptoms, and it is important for health care providers that attend PCS patients to consider the mental health of their patients. For example, there is a greater risk of suicide in military veterans that have suffered a TBI than those veterans who have not (11). We understand that depression, anger control issues, impairment of cognition and increased incidence of suicide are recognized as a diagnostic feature of chronic traumatic encephalopathy after concussion (12).

An increase in symptoms after concussion does not appear to be related to abnormal structural MRI and microstructural white matter findings. The significant predictors of PCS at 1 month include preinjury mental health problems and the presence of extracranial bodily injuries rather than structural brain disorders (13, 14). We are faced with a public that is exposed to a variety of information specific to head injury in the media with some accurate and inaccurate reporting that may confound treatment applications. Mental health issues have been reported in the media and have contributed to an increased anxiety by PCS patients and their families (15) who are concerned with long-term deficits in cognition and mental health as a consequence of medical mismanagement of concussions (16). Patients and their relatives want to know how long it takes to recover from a concussion. They desire to know if they might have permanent damage to their brains and long-term PCS patients will commonly question if they will ever recover.

Incapacitating PCS symptoms are reported by a majority of children and adolescents within 5 days after a concussion, but 90% arrive at a state of normality for PCS and neurocognition a month after their injury (17). The physical components of PCS are more easily understood and recognized than the neuropsychiatric components (18) even though we know higher rates of depressive symptoms exist in PCS patients when they are compared to the overall population (19).

We are concerned with the global health of our patients with PCS and recognize an ethical obligation of health care providers to protect the present and future mental and physical well-being of their patients (20). Most health care providers do not use instruments to measure or provide a baseline of mental health (21), perhaps because we expect most patients to return to a reasonable quality of life within 6 months of an mTBI. The long time PCS sufferers typically have had persistent symptoms with modifiable psychological risk factors for 1 month (i.e. distress, traumatic stress, and/or low resilience), and at 6 months, they can expect an increase in PCS, depression, traumatic stress, fatigue, insomnia, and a worsening of their quality of life (22).

We desired to study the physical and mental health of subjects that had severe debilitating PCS of greater than 6 months duration. We also wanted to evaluate the effectiveness of a novel PCS treatment in ameliorating both physical and mental health issues. The majority of our long-term symptomatic PCS patients had been treated with a variety of combinations of rest, rehabilitation, and pharmacy that had not been successful. It is understood that the management of sports concussion patients whose symptoms persist greater than 10 days should include cognitive, vestibular, physical, and psychological therapy (23) and we embrace these recommendations.

We understand that the functional integrity of the brain is closely related to eye movement function and that function is compromised postacutely in mCHI especially for saccades, antisaccades, smooth pursuit, and memory-guided sequences (5). We have observed similar cervical–vestibular–ocular pathology in our chronic PCS patients and have developed novel head–eye vestibular motion (HEVM) strategies that have been successful in patient outcomes (24–27). We wanted to measure the consequence of our treatment on both the physical and mental health functions of our sports PCS population. We needed powerful instruments that would provide us with validated outcomes of measurement of our PCS patient’s status and function before and after our therapy. We had experience using the C3 Logix integrated concussion management system developed at the Cleveland Clinic (28) and had found it to be ideal for our patient’s needs. The C3 Logix platform also collects data on the mental health status of PCS patients and is ideal to ascertain whether an HEVM physical rehabilitation modality might be associated with changes in mental health characteristics of PCS patients.

Materials and Methods
This study was a single-center, retrospective review of records performed at our Institutional Brain Injury Clinic conducted in accordance with the Declaration of Helsinki with equipoise. The records review was approved by the Carrick Institute Institutional Review Board (HHS #: IRB00006615 FWA: 00022305), and written informed consent was obtained from each patient prior to his or her examination and treatment. We identified PCS patients that were disabled from work or school for a period of time exceeding 6 months after suffering a sports concussion. These subjects all were enrolled in a 5-day HEVM rehabilitation program at our Institutional Brain Center with pre- and post-C3 Logix testing outcomes. The review was done by blinded investigators that were not involved in the treatment of subjects nor had any interaction with them or the treating physicians. The C3 Logix integrated concussion management system (28) was used before and after a 1-week HEVM rehabilitation program.

All subjects had their eye and head movements analyzed with Micromedical Technologies Visual Eyes (29) video oculography and a multisensory head–eye (JAZZ-nova) measurement system (30) during the tracking of a sinusoidal smoothly moving visual target in the horizontal and vertical planes. The primary treatment was gaze stabilization exercises administered with coordinated HEVM at positions and speeds associated with a decomposition of head and eye tracking movements. Subjects would attend to a visual target that would move in a plane at a velocity approximating the speed of head–eye decomposition while moving their head in combinations of pitch, yaw, and roll. The visual target underwent a gradual increase of its velocity and amplitude until head–eye movements further degraded or became synchronous at which time the session would stop. These sessions had durations of 3 min at a time followed by a 3-min rest and then repeated three times. The sessions would be scheduled five times per day with a rest period of a minimum of 1.5 h between sessions over 5 days.

Head, eye, and body movements were coordinated by using the Dynavision D2 visual, neurocognitive and rehabilitation system (31). Patients would use coordinated head–eye–body movements to “hit” 64 illuminated random targets encompassing a full visual field. The Dynavision D2 is gamified and trains reaction times and progresses neurocognitive abilities by providing output of reaction and accuracy scores. Patients would train on the Dynavision D2 three times per day for 10 min a session.

A secondary treatment of vestibular and somatic stimulation was administered by placing the patient in an accelerated rotation in a multiaxis rotational chair (MARC) (32) from 0 to 60°/s over 15 s about a plane opposite to the plane of head movements that were slower than coordinated eye movements in combined slow visual pursuits. Subjects underwent 3–30 s acceleration–deceleration rotations with the accelerated rotations beginning at 0 and terminating at 60°/s over 15 s followed by a 15-s deceleration from 60 to 0°/s. The acceleration–deceleration was linear and followed by a 2-min break between each rotation and repeated two times per day over 5 days.

A tertiary treatment of somatic sensory motor movements involved subject complex movements of the upper and lower extremity, both passively with a therapist and actively (right arm, left arm, right leg, and left leg) and in combination (right arm-left leg, left arm-right leg, right arm-right leg, and left arm-left leg). Subjects participated in somatic sensory motor movements for three sessions per day. The eye should not move if the head moves at the same speed of a slow moving target while fovealizing on the target. Neck musculature that exhibits increased tone or resistance to stretch and movement results in a sensory mismatch between head and eye movement. Manipulation of the cervical spine was administered to all patients on the side opposite the greatest eye movement observed with coordinated head eye targeting of slow pursuit targets in the horizontal plane.

C3 Logix Comprehensive Concussion Management System
C3 Logix consists of seven modules for evaluation, which take approximately 17 min to preform. Four modules are based on long-standing traditional tests that have been translated to electronic form in various incarnations, including the Concussion Symptom Assessment Survey (27 questions on physical condition), standardized assessment of concussion (SAC; including delayed recall), The Trails Test (with and without set switching), and The Processing Speed Task (symbol digit modalities test). The four additional modules include Balance testing (BESS Protocol while capturing accelerometer and gyroscope data and assessing sway volume as well as the standard BESS error score), Simple and Choice Reaction Time and Static and Dynamic Visual Acuity.

Patient symptoms were collected using the C3 Logix graded symptom checklist, derived from 22 standard, publicly accepted symptom survey questions following the recommendation of the 4th International Conference on Concussion in Sport held in Zurich (33). In addition, based on the Cleveland Clinic roll out experience, five extra questions were added to disaggregate the more subtle components of an examinees symptomology (34). The SAC (35, 36) is included in the C3 Logix platform and is derived from existing tests that look at immediate memory, delayed recall, orientation, and concentration.

Statistical Analysis
Statistical analysis was performed with STATA 14, Statacorp LP, College Station, TX, USA. Two sample paired t tests with equal variances were calculated for each variable independent of other variables. The effect size was calculated by Cohen’s d to indicate the standardized difference between two means. A Cohen’s d of 0.2 is considered to be a small effect size, 0.05 a medium effect size, and 0.08 a large effect size. Multiple regression models of the predictors of severity scores pre- and post-HEVM treatment were calculated as well as the semipartial R2 of the correlations of symptom severity with each variable to estimate only the unique effect of each predictor in the C3 Logix diagnostic battery. We wanted to know the effect of individual variables as predictors of the symptom severity score and calculated the semipartial R2 of the correlations of symptom severity with each variable. The semipartial R2 estimates only the unique effect of each predictor in the C3 Logix diagnostic battery. It is a conservative estimate of the effect of each variable because it measures only how much the R2 increases when that variable is entered after all the other variables are already in the model controlling for all of the other independent variables.

Results
We identified 620 subjects suffering from PCS and 70 subjects met the criterion of having persisting debilitating symptoms greater than 6 months, 45 males and 25 females with a mean age of 28 years (SD 8.48). There was a minimum age of 14 and a maximum age of 47. The males had a mean age of 28 years (SD 8.80 minimum age of 14 and a maximum age of 47). The females had a mean age of 29 (SD 8.036 minimum age of 18 and a maximum age of 47). The sports concussions were associated with a variety of activities including ice hockey, lacrosse, American football, soccer, skating, skiing, snowboarding, and gymnastics. A two sample unpaired t test with equal variances [t (68) = −0.7615, p = 0.4490] revealed that there were no statistically significant differences between the symptoms of males and females before HEVM treatment. Post-HEVM treatment demonstrated that there were no statistically significant differences in symptom outcomes between genders after treatment [t (68) = −0.0994, p = 0.9211]. Therefore, males and females were combined for all statistical analysis.

A paired t test of the symptom severity scores demonstrated a statistically significant decrease in severity scores after HEVM treatment [t (69) = 8.8844, p = 0.0000] with a large effect size (Cohen’s d = 0.83, 95% CI = 0.4879457–1.179151). A Cohen’s d is considered to be small if ≤0.2, medium if ≤0.5 and large if ≥0.8. A paired t test of the SAC scores demonstrated a statistically improvement in SAC scores after HEVM treatment [t (69) = −2.2663, p = 0.0266] with a small effect size (Cohen’s d = −0.2599813, 95% CI = −0.5922232–0.073194). Figure 1describes the symptom severity and SAC scores pre- and post HEVM therapy.