In a new study, published in Mayo Clinic Proceedings, researchers from Michigan Medicine find adults with spinal cord injury are at a higher risk of developing mental health disorders, including depression and anxiety, compared to adults without the condition.
The research team examined insurance claims data for adults, both with traumatic spinal cord injury and those without the condition, enrolled in a health insurance plan for at least three consecutive years and their diagnosis of a mental health disorder.
In particular, they found adults with spinal cord injury had a higher incidence of anxiety disorders (19.3% vs 14.1%), depressive disorders (29.3% vs 9.3%), and psychological multimorbidity, or having more than two mental health conditions (37.4% vs 23.9%), as compared to adults without spinal cord injury.
“We also found that individuals with spinal cord injury had an increased risk of developing other chronic diseases, including cardiovascular and pulmonary diseases, diabetes, liver disease, cancer, arthritis, circulatory conditions and electrolyte disorders,” says Mark Peterson, Ph.D., M.S., FACSM, the Charles E. Lytle, Jr. Research Professor in physical medicine and rehabilitation at Michigan Medicine and the lead author of the study.
“Which makes sense, as patients with spinal cord injuries have extreme sedentary behavior including prolonged bed rest after injury.”
Denise Tate, Ph.D., ABPP, FACRM, a professor of physical medicine and rehabilitation at Michigan Medicine and the senior author of the study, notes that much of the past research regarding spinal cord injury focuses on physical health outcomes.
She says this study highlights the need for understanding this patient population’s mental health and clinical care needs, as they’re critical to overall quality of life and well-being in patients with spinal cord injury.
Peterson agrees, “Clinicians caring for adults with spinal cord injury need to be aware of the increased risk of developing mental health disorders in this patient population. This may be particularly important during these recent times of social distancing due to COVID-19, as these patients often already experience social isolation.”
Cognitive impairment and dementia
In a recent case-control study with 150 SCI participants, it what reported that approximately one third of individuals with SCI experienced varying degrees of cognitive dysfunction .
Patients with SCI were at a 13 times greater risk for having impaired cognition as compared with controls . Different forms of cognitive impairment, such as difficulty processing information and abstract thinking, inability to learning new skills, and impaired concentration and memory, were reported in SCI patients .
Improving cognitive deficits due to SCI has been the aim of some clinical trials, one of which investigated the effect of 12-week anti-inflammatory diet on verbal learning and memory.
The results showed no significant cognition improvement after the intervention, despite a considerable decrease in pro-inflammatory cytokine levels . Phillips et al. reported that low blood pressure (BP) in individuals with high-level SCI may partially mediate cognitive dysfunction.
They observed the effect of midodrine in 10 individuals with SCI higher than the T6 spinal segment, showing that retaining BP to 85 ± 10 mmHg was associated with approximately 15% improvement in cognitive function (P < 0.05), which was also proportional to the increase of the resting BP as a result of midodrine .
Dementia is a term used to describe symptoms associated with progressive loss of cognitive function. Alzheimer’s disease (AD) is by far the most common type of dementia. Two recent studies investigated the association between SCI and dementia [18,19].
One study enrolled 941 SCI individuals and 5,060 controls and reported an increased risk of dementia in the SCI group (crude hazard ratio (HR): 1.91 (95% confidence interval (CI): 1.38–2.63)).
The higher risk of dementia was still observed after adjusting for age, sex, diabetes mellitus, hyperlipidemia, hypertension, autoimmune disorders, affective psychosis, coronary heart disease, stroke, traumatic brain injury, and Parkinson’s disease (HR: 1.94 (95%CI: 1.41–2.67, P-value<0.001)).
However, no statistically significant difference was noted for specifically developing AD (adjusted HR: 1.78 (95%CI: 0.69–4.48)) . However, another study included 9,257 SCI patients and 555,390 controls, and the results indicated an increased risk of developing AD in individuals with SCI (HR: 1.71 (95%CI: 1.06–2.76)) .
Multiple sclerosis (MS)
Multiple sclerosis is considered a chronic immune-mediated neurological disorder that results in the destruction of both white and gray matter. Lin et al. performed a cohort study investigating the association between SCI and MS .
The study included 11,913 participants with SCI and over 59,565 controls matched for sex, age, pre-existing comorbidities (diabetes mellitus, hypertension, and dyslipidemia), and socioeconomic status (geographical region, level of urbanization, and income level). Within the median follow-up time of 30 months, 5 MS events were reported among the SCI group (0.041%) compared to 4 events in the non-SCI group (0.006%).
The incidence rate of MS in SCI patients was approximately 18 per 100,000 person-years (vs. 2.82 per person-years in non-SCI individuals). They also reported an over eightfold-increased risk of developing MS among patients with SCI (HR: 8.33, 95%CI: 1.99–34.87,P < 0.05).
The co-occurrence of SCI and MS can be a great dilemma for clinicians. On one side, SCI manifestations can mask the typical symptoms of MS which lead to a significant delay in MS diagnosis.
On the other side, this co-existence can considerably affect the patient’s quality of life. To date, the number of human studies regarding this correlation is limited and the underlying mechanisms are unclear. It can be speculated that neuroinflammation due to SCI may increase the risk of MS, but there is scarce evidence to support this supposition thus far.
Parkinson’s disease (PD)
Parkinson’s disease is the most common neurodegenerative movement disorder, and is caused by the degeneration and death of dopaminergic neurons. One study evaluated the occurrence of PD in persons with SCI, comparing 10,125 participants in the SCI group versus 10,125 non-SCI individuals .
It was found that within 30 months of follow-up, 99 persons in SCI group (0.98%) and 59 in non-SCI group (0.58%) developed PD. The incidence rate of PD among SCI cases was approximately 4 per 1000 person-years (versus 2.5 per 1000 person-years among non-SCI persons).
After adjustment for sex, age, comorbidities (including diabetes, hypertension, dyslipidemia, stroke, and coronary heart disease), as well as socioeconomic status (including income, geographical region, and levels of urbanization), it was found that the risk of PD occurrence among SCI patients within the first year of follow-up was 1.39-fold higher than controls, although it was not statistically correlated (95%CI: 0.87–2.29).
However, after the first year, risk of PD was statistically associated with SCI (hazard risk (HR), 95%CI: 2.05, 1.19–3.55). The overall risk of PD was 1.65-fold greater among SCI participants (95%CI: 1.16–2.33).
It is now recognized that α-synuclein, a small presynaptic neuronal protein with 140 amino acids, is a central component to the pathogenesis of PD . The structural changes in this protein may lead to autoimmune responses targeting dopaminergic neuronal cells and cause PD. Synuclein expression can be induced due to SCI, which may justify this correlation [22,23]. Further studies should investigate this association and the possible underlying mechanisms for this correlation.
Restless leg syndrome (RLS)
Restless leg syndrome or Willis-Ekbom disease is a chronic progressive movement disorder of the limbs which is characterized by an urge to move the legs accompanied by unpleasant sensations at rest. About 2%–3% of people in the US suffer from RLS .
Some prior studies with a small number of SCI patients reported the co-occurrence of RLS and SCI [, , , ]. A case survey of 195 individuals with SCI showed that RLS occurs frequently (17.9%) in SCI patients, and RLS usually responds well to dopaminergic treatment .
It was also appreciated that RLS developed within the first year following SCI in most of the cases. Moreover, it appeared mostly in people with lumbosacral lesions. In line with this study, another study consisting of 162 SCI cases reported a similar prevalence of RLS, but it was found that RLS developed in most cases with both cervical and thoracic SCI .
The diagnosis of RLS in patients with SCI could be confusing. Differentiation between neuropathic pain and RLS is challenging and the treatment-resistant sensory motor symptoms of SCI patients could be the signs of RLS .
Overall, the main complaint of SCI patients with RLS was reported to be tingling in the legs, followed by burning and sense of an electric shock. In those who were not able to move their legs, symptoms could be relieved by rubbing, massage, or washing the legs with cold water. Passive movement of lower extremities or moving the trunk back and forth was also found to be useful [27,29]. It was reported that Pramipexole, as a dopamine agonist, can significantly improve RLS symptoms in SCI cases [27,28].
Provoked seizures may occur in SCI individuals in the context of autonomic dysreflexia occurrence. Prior studies investigating the clinical features of autonomic dysreflexia in patients with SCI indicated that about 1% of this population had acute seizures [31,32].
However, no characteristic aspects of seizures were reported in these studies. Four case-reports also described the co-occurrence of convulsive/focal seizures and autonomic dysreflexia in SCI individuals [, , , ].
Posterior reversible encephalopathy syndrome (PRES) could be the cause of the seizure. PRES is a condition characterized by transient and sudden onset of seizures, headaches, and visual loss accompanied by abnormalities on T2 fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) in the brain. Severe hypertensive episodes are correlated with increased risk of PRES. The concomitance of SCI, PRES, autonomic dysreflexia, and convulsion has been reported [35,36].
Long-term outcomes in patients experiencing seizures due to autonomic dysreflexia were reported to be poor. One clinical review evaluated life-threatening outcomes associated with autonomic dysreflexia and demonstrated that 39% of those complications were seizure or convulsions, which was the second most frequent CNS-related complication after hemorrhage .
Seizure was also reported in SCI patients without autonomic dysreflexia. Two case-reports described the presence of epilepsy in SCI subjects. Bu et al.  reported a male with old odontoid fracture and atlantoaxial dislocation and spinal cord compression experienced grand mal seizures and Lavy et al.  described a case with clonic convulsions of the upper limbs and grand mal attacks after a high thoracic traumatic spinal cord lesion. No symptom of autonomic dysreflexia was recognized in these cases and the underlying mechanisms were unclear.
Other neurological disorders
The presence of pre-existing neurological manifestations of SCI, such as paraplegia/tetraplegia and paresis, may mask typical patterns of skeletal muscle impairment of MG and GBS and cause significant delay for the diagnosis of these disorders.
|Study identifier||Year of publication||Country||No of case||Age (year)||Gender||Results|
|Grant et al. .||2011||Canada||1||31||Male||After sepsis occurrence the patient developed flaccidity and facial diplegia and paraclinical tests showed GBS which get treated by IVIg|
|Scozzafaya et al. ||2008||Canada||1||28||Male||After SCI and shortly after admission due to injury marked autonomic instability, fluctuating temperature and severe hypotension occurred which accompanied by lower weakness and new weakness in face and upper extremities. Six months after GBS treatment the patient weakness in face got better.|
|Son et al. ||2011||South Koreas||1||50||Male||After admission due to SCI patient first, suffered abdominal pain; followed by numbness in hands, chest discomfort, dyspnea, facial weakness and areflexia which GBS was diagnosed. IVIg was used and in two months neurological dificits got treted|
|Gounden et al. ||2016||Australia||1||61||Male||A patient with tetraplegia due to SCI had sudden onset of diplopia and bilateral ptosis. Acetylcholine receptor antibody was negative but EMG showed muscle fatigue. Ocular signs respond to pyridostygmine.|
|Lin et al. ||2008||Taiwan||1||N/A||Male||Previous case of myasthenia gravis had SCI and later, due to pneumonia and urinary tract infection the signs and symptoms of myasthenia gravis returned which got treated|
|Kolli et al. ||2011||UK||1||54||Male||A paralyzed person for 40 years admitted for surgery of sacral pressure sore. During admission diplopia, fluctuating dysphagia, and slurred speech occurred. EMG and response to pyridostigmine confirmed MG diagnosis. The patient died in six weeks due to cardiorespiratory arrest.|
|Kaux et al. ||2009||Belgium||1||92||Male||Major swallowing disorder occurred in a quadriplegic patient which MG diagnosis was achieved after performance of EMG.|
University of Michigan