Cervical muscle stiffness and parasympathetic nervous system improvements for treatment-resistant depression.

BACKGROUND: Although treatment-resistant depression (TRD) is a major public health problem that increases mortality due to suicides, a considerable percentage of patients do not respond adequately to variable treatments. Patients with TRD sometimes have comorbid cervical stiffness. This observational study aims to examine the association of local modulation of cervical muscles with TRD and to learn the involvement of the parasympathetic nervous system in the underlying mechanism. METHODS: A total of 1103 hospitalized patients with TRD who were resistant to outpatient care were enrolled between May 2006 and October 2021. All patients underwent local modulation of the cervical muscles by physical therapy during hospitalization. The presence or absence of TRD and whole-body disorders, such as headache, dazzling, cervical stiffness, and cardiovascular and gastrointestinal disorders, was determined by the patient's subjectivity using the self-rated medical interview sheet at admission and discharge. Pupil light reflex parameters were also measured at admission and discharge using a binocular infrared pupilometer. RESULTS: The improvement rate of TRD during hospitalization was 72.1%, and did not differ significantly by sex, age, and hospitalization period. The improvement of TRD showed a strong association with those of cervical stiffness and dazzling, a pupil light reflex disorder (p < 0.001: odds ratios = 12.76 and 6.39, respectively), but not with those of headache or cardiovascular and gastrointestinal disorders (p > 0.05). In the TRD-improved patients, the pupil light reflex parameters representative of the parasympathetic nervous system function ameliorated: pupil diameter decreased, while constriction rate and velocity increased during hospitalization. In contrast, little amelioration of the parameters was seen in the TRD-unimproved patients. CONCLUSIONS: Cervical muscle stiffness may be associated with TRD, possibly through dysfunction of the parasympathetic nervous system. TRIAL REGISTRATION: ID: UMIN000040590. First registration date: 30/05/2020.

Possible involvement of the autonomic nervous system in cervical muscles of patients with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS).

BACKGROUND: Patients with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) sometimes present with stiffness of the cervical muscles. To investigate the pathophysiology of ME/CFS, this observational study compared patients with versus without recovery from ME/CFS through local modulation of the cervical muscles. METHODS: Over a period of 11 years, a total of 1226 inpatients with ME/CFS who did not respond to outpatient care were enrolled in this study. All patients received daily cervical muscle physical therapy during hospitalization. Self-rated records documenting the presence or absence of ME/CFS, as well as the representative eight symptoms that frequently accompany it at admission and discharge, were compared. Pupil diameter was also measured to examine autonomic nervous system function involvement. RESULTS: The recovery rate of ME/CFS after local therapy was 55.5%, and did not differ significantly by sex, age strata, and hospitalization period. The recovery rates of the eight symptoms were variable (36.6-86.9%); however, those of ME/CFS in the symptom subpopulations were similar (52.3-55.8%). The recovery rates of all symptoms showed strong associations with that of ME/CFS (p < 0.001). The pupil diameter was more constricted in the ME/CFS-recovered patients than in the ME/CFS-unrecovered patients in the total population and the subpopulations stratified by sex, age, and hospitalization period. CONCLUSIONS: There was a strong association between the recovery of ME/CFS and other related whole-body symptoms. The recovery of ME/CFS may be partly linked to amelioration of the autonomic nervous system in the cervical muscles. TRIAL REGISTRATION: UMIN000036634 . Registered 1 May 2019 - Retrospectively registered.

Cervical muscle diseases are associated with indefinite and various symptoms in the whole body.

PURPOSE: Patients with various and indefinite symptoms in the whole body occasionally have coincident with stiffness or tenderness of the cervical muscles. This prospective case series examined the effect of local modulation of the cervical muscles in patients with cervical disorders reporting indefinite whole-body symptoms. METHODS: A total of 1863 hospitalized patients with cervical disorders accompanying three or more indefinite whole-body symptoms, who were resistant to outpatient care, were enrolled in this study for 12 years. All patients underwent daily physical therapies to the cervical muscles during hospitalization. Self-rated records on the medical interview sheets documenting 30 representative symptoms including cervical/shoulder pain or stiffness and 28 representative indefinite whole-body symptoms at admission and discharge were compared across the population. RESULTS: The number of symptoms decreased significantly with the local modulation of the cervical muscles during hospitalization. All of the 28 indefinite whole-body symptoms at admission showed recovery rates greater than 50% at discharge. The mean number of symptoms decreased significantly from 17.8 at admission to 7.4 at discharge (p < 0.0001). The percentages of patients reporting 10 or more symptoms were 91.1% and 29.3% at admission and discharge, respectively. Moreover, 8.2% of patients reported no residual symptoms at discharge. CONCLUSION: Cervical muscle lesions may contribute to indefinite whole-body symptoms, possibly through dysfunction of the parasympathetic nervous system in the muscles. Local modulation of cervical muscles could lead to a breakthrough in the management of patients with indefinite whole-body symptoms. TRIAL REGISTRATION ID: UMIN000035445. These slides can be retrieved under Electronic Supplementary Material.

Effect of intensive inpatient physical therapy on whole-body indefinite symptoms in patients with whiplash-associated disorders.

BACKGROUND: A considerable number of patients with whiplash-associated disorders (WAD) report variable and indefinite symptoms involving the whole body, despite there being no evidence of direct injuries to organs other than the neck. However, little is known about their management or underlying mechanism. This study examined the effect of intensive physical therapy at the cervical muscles in patients with WAD reporting whole-body indefinite symptoms. METHODS: A total of 194 hospitalized patients with WAD who were resistant to outpatient care by reporting whole-body indefinite symptoms between May 2006 and May 2017 were enrolled in this observational study. All patients underwent daily physical therapies by low-frequency electric stimulation therapy and far-infrared irradiation to the cervical muscles during hospitalization. Self-rated records in the medical interview sheets on 22 representative whole-body symptoms at admission and discharge were compared. RESULTS: The number of symptoms was markedly decreased by the physical therapies during hospitalization. Almost all symptoms showed recovery rates of more than 80% at discharge as compared to those at admission. Although the percentage of patients reporting at least four of the 22 representative indefinite symptoms was 99.0% at admission, it decreased to 7.7% at discharge. Sixteen percent of patients recovered completely without any residual symptoms. The mean number of symptoms significantly decreased from 13.1 at admission to 2.0 at discharge. Notably, symptoms other than those in the neck or shoulder recovered to a greater extent than those in the neck or shoulder. CONCLUSIONS: This study, for the first time, examined the management of whole-body indefinite symptoms in patients with WAD. The intensive physical therapy markedly improved the symptoms, suggesting the involvement of cervical muscles in the pathogenesis. TRIAL REGISTRATION: UMIN000035435 (Retrospectively registered on Jan 3, 2019).

Cervical neuro-muscular syndrome: discovery of a new disease group caused by abnormalities in the cervical muscles.

Our previous study of whiplash injury found that abnormalities in the cervical muscles cause autonomic dystonia. Further research has found that abnormalities in the cervical muscles cause headache, chronic fatigue syndrome, vertigo, and dizziness. We named this group of diseases cervical neuro-muscular syndrome. Patients treated within a 2-year period from April 1, 2002 to March 31, 2004 reported good outcomes in 83.8% for headache, 88.4% for vertigo and dizziness, 84.5% for chronic fatigue syndrome, 88.0% for autonomic dystonia, and 83.7% for whiplash-associated disorder. A large number of outpatients present with general malaise, including many general physical complaints without identifiable cause. We propose that treatment of the cervical muscle is effective for general malaise.

Correlation of histology and molecular genetic analysis of 1p, 19q, 10q, TP53, EGFR, CDK4, and CDKN2A in 91 astrocytic and oligodendroglial tumors.

PURPOSE: The histological diagnosis of human gliomas is of great importance for estimating patient prognosis and guiding therapy but suffers from being subjective and, therefore, variable. We hypothesized that molecular genetic analysis could provide a more objective means to classify tumors and, thus, reduce diagnostic variability. EXPERIMENTAL DESIGN: We performed molecular genetic analysis on 91 nonselected gliomas for 1p, 19q, 10q, TP53, epidermal growth factor receptor, and cyclin-dependent kinase 4 abnormalities and compared with the consensus diagnoses established among four independent neuropathologists. RESULTS: There were six astrocytomas, seven anaplastic astrocytomas, 45 glioblastomas, 21 oligodendrogliomas, eight anaplastic oligodendrogliomas, three oligoastrocytomas, and one anaplastic oligoastrocytoma. Twenty-nine cases had either 1p or 19qloss of heterozygosity (LOH) while retaining both copies of 10q, of which 25 (86%) were histologically oligodendroglioma, anaplastic oligodendroglioma, oligoastrocytoma, or anaplastic oligoastrocytoma. As for the oligodendroglial tumors, unanimous agreement of the initial diagnoses was almost restricted to those cases with combined 1p/19qLOH, whereas all nine tumors without 1p loss initially received variable diagnoses. Interestingly, TP53 mutation was inversely related to 1pLOH in all gliomas (P = 0.0003) but not 19qLOH (P = 0.15). CONCLUSIONS: These data demonstrate that molecular genetic analysis of 1p/19q/10q/TP53 has significant diagnostic value, especially in detecting oligodendroglial tumors. In addition, 1pLOH and TP53 mutations in gliomas may be markers of oligodendroglial and astrocytic pathways, respectively, which may separate gliomas with the same histological diagnosis, especially oligodendroglial tumors and glioblastomas. Testing for those molecular genetic alterations would be essential to obtain more homogeneous sets of gliomas for the future clinical studies.