Dysautonomia, Hypermobility Spectrum Disorders and Mast Cell Activation Syndrome as Migraine Comorbidities.

PURPOSE OF REVIEW: Dysautonomia refers to the dysfunction of the autonomic nervous system and encompasses a wide variety of autonomic symptoms and disorders. The most common autonomic disorders are postural orthostatic tachycardia syndrome (POTS), neurocardiogenic syncope (NCS), and orthostatic hypotension (OH), which may be encountered in clinical practice as part of a triad of dysautonomia, hypermobility spectrum disorders (HSD), and mast cell activation syndrome (MCAS). Migraine is one of the most common comorbidities of POTS, HSD, and MCAS; conversely, these conditions are also prevalent in patients with migraine, especially in those with multiple systemic symptoms, such as chronic dizziness, lightheadedness, orthostatic intolerance, joint pain, and allergic symptoms. Diagnostic criteria, pathophysiologic mechanisms, and therapeutic considerations in patients with migraine and comorbid dysautonomia, HSD, and MCAS are reviewed. RECENT FINDINGS: Numerous studies indicate a significant overlap and shared pathophysiology in migraine, dysautonomia, HSD, and MCAS. In clinical setting, dysautonomia, HSD, and MCAS may present a diagnostic and therapeutic challenge in patients with migraine and require a high index of suspicion on the part of the neurologist. Diagnosis and treatment of these complex disorders in patients with migraine is essential to comprehensive patient-centric care, reduced symptom burden, and improved functional impairment secondary to both migraine and comorbidities.

Autonomic nervous system involvement in chronic inflammatory demyelinating polyradiculoneuropathy: a literature review.

BACKGROUND AND AIMS: Although dysautonomia is a well-recognized complication of acute demyelinating polyradiculoneuropathy, it is rarely reported and evaluated in chronic demyelinating neuropathies. The purpose of this review is to search and synthesize the current literature on the prevalence and type of autonomic dysfunction (AD) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). METHODS: PubMed and Web of Science were searched for studies reporting AD in CIDP. RESULTS: Twelve studies, including 346 patients with CIDP, were found eligible for the review. Seven studies used autonomic tests only as an additional component of the comprehensive clinical evaluation, and found that dysautonomia in CIDP may indicate the presence of a comorbid disease (e.g., diabetes) and facilitate the differentiation of CIDP from other neuropathies (e.g., amyloid neuropathy). Five studies performed quantitative assessment of autonomic function in CIDP as a primary goal. Two studies have used the Composite Autonomic Severity Score (CASS) to assess severity and distribution of dysautonomia. The reported prevalence of dysautonomia in CIDP during quantitative assessment of autonomic function ranged from 25 to 89%, depending on the battery of tests used, with CASS not exceeding 4 points. The abnormalities in autonomic tests indicated both sympathetic and parasympathetic dysfunction and did not correlate with the duration, severity and variant of CIDP. CONCLUSIONS: Clinical or subclinical involvement of the ANS has been shown to be common and relatively mild in CIDP. The impact of autonomic impairment on disability and of its possible response to therapy in CIDP needs to be further investigated.

Subtle differences in autonomic symptoms in people diagnosed with hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorders.

The hypermobile Ehlers-Danlos syndrome (hEDS) GENE study is a multicenter, cohort study with the goal to identify genes associated with hypermobile EDS. Of the 148 people enrolled in the hEDS GENE study, 98 meet the 2017 hEDS criteria, 27 have a hypermobility spectrum disorder (HSD) and 23 are asymptomatic family members. More than 80% of participants are female with an average age of 41 years. Each participant has completed seven questionnaires to quantify disease-related symptomatology. People with hypermobility experience a variety of physical and somatic symptoms, especially in the areas of fatigue, kinesiophobia, gastrointestinal, and autonomic function. These cause a significant decrease in health-related quality of life. The frequency and severity of most symptoms were indistinguishable between participants with hEDS and HSD; however, there were significant differences in autonomic symptoms. Less than 20% of participants had autoantibodies known to be associated with dysautonomia. Subtle symptomatic differences in people meeting the 2017 diagnostic criteria suggest focusing further etiologic studies on autonomic pathways.

Human papillomavirus (HPV) vaccine and autonomic disorders: a position statement from the American Autonomic Society.

INTRODUCTION: Human papillomavirus (HPV) vaccination has been anecdotally connected to the development of dysautonomia, chronic fatigue, complex regional pain syndrome and postural tachycardia syndrome. OBJECTIVES: To critically evaluate a potential connection between HPV vaccination and the above-noted conditions. METHODS: We reviewed the literature containing the biology of the virus, pathophysiology of infection, epidemiology of associated cancers, indications of HPV vaccination, safety surveillance data and published reports linking HPV vaccination to autonomic disorders. RESULTS: At this time, the American Autonomic Society finds that there are no data to support a causal relationship between HPV vaccination and CRPS, chronic fatigue, and postural tachycardia syndrome to other forms of dysautonomia. CONCLUSION: Certain conditions are prevalent in the same populations that are vaccinated with the HPV vaccine (peri-pubertal males and females). This association, however, is an insufficient proof of causality.

Alcohol-induced autonomic dysfunction: a systematic review.

PURPOSE: Autonomic dysfunction is a known consequence of chronic and excessive alcohol consumption. The aim of this systematic review was to characterise this phenomenon, describe the frequency at which it occurs and to explore the best management strategies. METHODS: A systematic, computer-based search was conducted using the PubMed database. All studies identified by the search were evaluated independently by at least three authors. For inclusion, studies had to report human subjects consuming ethanol in excess. Case reports and non-original studies were excluded from this review. RESULTS: A total of 55 studies were included in this review. According to cardiovascular reflex tests, 16-73% of chronic alcohol abusers suffer from autonomic dysfunction. The most commonly occurring symptom is erectile dysfunction, whilst other features such as postural dizziness are rare. The most important risk factor for this condition is total lifetime dose of ethanol, although there is mixed evidence supporting the role of other risk factors. The only management strategy currently explored in the literature is abstinence, which appears to lead to significant improvement in autonomic investigations. CONCLUSION: Current literature includes studies of highly heterogeneous populations, consuming differing volumes of alcohol over variable periods of time and utilising a number of different autonomic test batteries and criteria to diagnose autonomic dysfunction. Therefore, further research using homogeneous methods for measuring autonomic dysfunction in the field is needed. Despite this limitation, our review demonstrated that autonomic dysfunction is very common among alcohol abusers.

Family aggregation analysis shows a possible heritable background of equine grass sickness (dysautonomia) in a Hungarian stud population.

Equine grass sickness (also known as dysautonomia) is a life-threatening polyneuropathic disease affecting horses with approx. 80% mortality. Since its first description over a century ago, several factors, such as the phenotype, intestinal microbiome, environment, management and climate, have been supposed to be associated with the increased risk of dysautonomia. In this retrospective study, we examined the possible involvement of genetic factors. Medical and pedigree datasets regarding 1,233 horses with 49 affected animals born during a 23-year period were used in the analysis. Among the descendants of some stallions, the proportion of animals diagnosed with dysautonomia was unexpectedly high. Among males, the odds of dysautonomia were found to be higher, albeit not significantly, than among females. Significant familial clustering (genealogical index of familiality, P = 0.001) was observed among the affected animals. Further subgroups were identified with significant (P < 0.001) aggregation among close relatives using kinship-based methods. Our analysis, along with the slightly higher disease frequency in males, suggests that dysautonomia may have a genetic causal factor with an X-linked recessive inheritance pattern. This is the first study providing ancestry data and suggesting a heritable component in the likely multifactorial aetiology of the disease.

Dysautonomia and Headache in the Pediatric Population.

Dysautonomia and headache are 2 common diagnoses within pediatric neurology; in the case of dysautonomia, a lack of consideration may lead to misdiagnosis. Despite being common conditions, there is a lot to learn about each individually as well as collectively. Many of the symptoms between headache and dysautonomia patients overlap making the diagnosis difficult. Migraine patients often exhibit symptoms of dysautonomia, namely postural orthostatic tachycardia syndrome (POTS); yet these symptoms are overlooked or lumped in as a part of their migraine diagnosis. The distinction or coexistence between dysautonomia and headache is identified through a thorough history, a full exam, and an open mind. This is crucial for the treatment and outcomes of these patients. Struggles arise when critical treatment differences are overlooked because dysautonomia is not considered. In this review, we will look at the epidemiology of dysautonomia and headache with focus on POTS and migraine. We will then compare the clinical features of both conditions as well as some hypothesized pathophysiology overlaps. We will conclude by summarizing the diagnostic approach and multitiered treatment options for POTS and migraine.

Stability of the HTLV-1 glycoprotein 46 (gp46) gene in an endemic region of the Brazilian Amazon and the presence of a significant mutation (N93D) in symptomatic patients.

BACKGROUND: The human T-lymphotropic virus type 1 (HTLV-1) affects 2-5 million people worldwide, and is associated with a number of degenerative and infectious diseases. The Envelope glycoproteins (gp) are highly conserved among the different HTLV-1 isolates, although nucleotide substitutions in the region that codifies these proteins may influence both the infectivity and the replication of the virus. The gp46 gene has functional domains which have been associated with the inhibition of the formation of the syncytium, cell-cell transmission, and the production of antibodies. The present study investigated the genetic stability of the gp46 gene of HTLV-1 in an endemic region of Brazilian Amazonia. METHODS: Index case (IC - a sample of a given family group) carriers of HTLV-1 were investigated in the metropolitan region of Belém (Pará, Brazil) between January 2010 (registered retrospectively) and December 2015. The sequences that codify the gp46 were amplified by PCR, purified and sequenced (MF084788-MF084825). The gene was characterized using bioinformatics and Bayesian Inference. RESULTS: The 40 patients analyzed had a mean age of 45.2 years and 70% presented some type of symptom, with a predominance of pain and sensitivity, dysautonomia, and motor disorders. All patients presented the aA (Transcontinental Cosmopolitan) genotype, with an extremely low mutation rate, which is characteristic of the codifying region (aA - 1.83 × 10-4 mutations per site per year). The gp46 gene had a nucleotide diversity of between 0.00% and 2.0%. Amino acid mutations were present in 66.6% of the samples of individuals with signs/symptoms or diseases associated with HTLV-1 (p = 0.0091). Of the three most frequent mutations, the previously undescribed N93D mutant was invariably associated with symptomatic cases. CONCLUSIONS: The aA HTLV-1 subtype is predominant in the metropolitan region of Belém and presented a high degree of genetic stability in the codifying region. The rare N93D amino acid mutation may be associated with the clinical manifestations of this viral infection. IMPORTANCE: Little is known of the phylogeny of HTLV-1 in the endemic region of Brazilian Amazonia, and few complete gene sequences are available for the gp46 glycoprotein from the local population. The nucleotide sequences of the viral gp46 gene recorded in the present study confirmed the genetic stability of the region, and pointed to a homogeneous viral group, with local geographic characteristics. Further research will be necessary to more fully understand the molecular diversity of this protein, given the potential of this codifying region as a model for an effective HTLV-1 vaccine. The identification of a rare mutation (N93D), present only in symptomatic patients, should also be investigated further as a potential clinical marker. TRIAL REGISTRATION: ISRCTN 12345678, registered 28 September 2014.

Allergy and high trait anxiety are related to increases in heart rate variability: results of naturalistic long-term design study.

Summary: A number of studies report heart rate variability (HRV) changes in allergic as well as high trait anxious people, and associations between allergic inflammation and trait anxiety. This study investigated HRV of 20 low anxious allergic, 19 healthy high trait anxious and 18 healthy low anxious, in naturalistic setting. On arranged research days, subjects performed measurements using portable ECG device and subjective self-assessment of perceived stress. Five repeated measurements data from each subject have shown increases in overall HRV, as well as HRV on respiratory frequencies in both allergy and high trait anxiety. Subject's sex was an important factor, because HRV increases in allergy were only apparent in women. Data from self-assessment show no differences in experienced stress attributable to allergy, only to trait anxiety.

Body weight and dysautonomia in early Parkinson's disease.

OBJECTIVES: Patients with Parkinson's disease (PD) begin to lose weight several years before diagnosis, which suggests weight variation is associated with some factor(s) that precede the onset of motor symptoms. This study aimed to investigate the association of autonomic nervous system with body weight in patients with PD. MATERIALS AND METHODS: The subjects were 90 patients with early de novo PD. We examined the associations of body mass index (BMI) with sympathetic nervous activity reflected in orthostatic intolerance or cardiac uptake of 123 I-metaiodobenzylguanidine and parasympathetic nervous activity reflected in constipation or heart rate variability (HRV). RESULTS: Twelve patients (13.3%) were overweight (BMI>25 kg/m2 ), 62 patients (68.9%) were normal-weight (18.5≦BMI<25 kg/m2 ), and 16 patients (17.8%) were underweight (BMI<18.5 kg/m2 ). Underweight patients had greater disease severity and decrease in blood pressure on head-up tilt-table testing, higher cardiac washout ratio of 123 I-metaiodobenzylguanidine, and lower HRV and complained of constipation more often than those with normal-weight or overweight patients. On multiple regression analyses, the correlation of these variables with BMI maintained statistical significance after adjustment for age, sex, symptom duration, and motor subtype. CONCLUSIONS: Dysautonomia and disease severity are closely related to body weight independently of age, sex, symptom duration, and motor subtype. Dysautonomia may play a partial role on weight variation in the early stage of PD.

Clinical Characteristics, Comorbidities and Hospital Outcomes in Hospitalizations with Cyclic Vomiting Syndrome: A Nationwide Analysis.

BACKGROUND: Data on cyclic vomiting syndrome (CVS) are limited to studies from tertiary care centers. There is a paucity of information about CVS on a national scale. AIM: To study the clinical characteristics, comorbidities, and hospital outcomes in patients hospitalized with CVS using a nationwide database. METHODS: We identified all hospitalizations associated with a primary diagnosis of CVS in 2010 and 2011 using the Nationwide Inpatient Sample with an age category of 18-55 years. A 1:2 random sample of non-CVS hospitalizations with the same age category was obtained, and comparisons between groups were made. Multivariate logistic regression analysis was used to determine comorbidities independently associated with CVS. RESULTS: Our study included 20,952 CVS and 44,262 non-CVS patients. CVS patients tended to be younger, male, and white compared to non-CVS patients. On multivariate analysis, CVS was significantly associated with comorbidities including dysautonomia, migraine, anxiety, marijuana use, irritable bowel syndrome, gastroparesis, gastroesophageal reflux disease, asthma, cigarette smoking, and hypertension. CVS patients underwent esophagogastroduodenoscopy, colonoscopy, and gastric emptying tests more frequently. They had more favorable hospital outcomes like more routine discharges (discharge to home/self-care), lower mortality, and shorter length of stay but tended to leave against medical advice more frequently. CVS patients incurred total hospital charges of about $400 million over the 2 years. CONCLUSIONS: Our study showed that CVS is associated with several comorbidities and incurred substantial health care costs despite benign outcomes. Efforts to optimize therapy of CVS, manage comorbid conditions and reduce healthcare utilization are warranted.

Drugs with potential cardiac adverse effects: Retrospective study in a large cohort of parkinsonian patients.

INTRODUCTION/OBJECTIVE: Drugs with potential cardiac adverse effects are commonly prescribed in Parkinson's disease (PD). To describe demographic and clinical characteristics in a group of PD patients with cardiac events and to evaluate risk factors. PATIENTS AND METHODS: We sampled 506 consecutive PD patients (211 women/295 men), median age 68.3±10.6 years (range 36-95) and median disease duration 11.2±6.5 years (range 1-49). Medications with potential cardiac effects, i.e. QT prolongation (citalopram, escitalopram, venlafaxine, sertraline, domperidone, amantadine, solifenacin), ventricular arrhythmia (rivastigmine, clozapine, midodrine, sildenafil, tadalafil) and ischemic heart disease (rasagiline, entacapone, tadalafil) were recorded. Demographic and clinical data were collected prospectively; cardiac events were obtained retrospectively. RESULTS: Twenty-four patients (4.7%) (9 women/15 men) presented a cardiac event. Fifteen (62.5%) patients had dysautonomia, 4 (16.6%) a history of heart disease and 8 (33.3%) were taking one or more drugs with a definite potential cardiac adverse effect. Age (75.9±6.6 yr vs. 67.8±11 yr), disease duration (14.7±3.6 yr vs. 11±6.5 yr), dysautonomia (62.5% vs. 24.5%) and dementia associated with PD (37.5% vs. 14.6%) were significantly higher in the group with cardiac events (P<0.05). Cofactors increasing the risk for cardiovascular events were age and dysautonomia. DISCUSSION/CONCLUSION: Our results indicate that the neurodegenerative process in Parkinson's disease is associated with a higher risk of cardiovascular complications.

Lower urinary tract dysfunction in patients with dysautonomia.

OBJECTIVE: With the goal of better defining the types of bladder dysfunction observed in this population, we present the chief urologic complaints, results of urodynamic studies, and treatments of patients with dysautonomia-related urinary symptoms. METHODS: All patients with dysautonomia referred to our neurourology clinic between 2005 and 2015 for management of lower urinary tract dysfunction were retrospectively reviewed. Each patient's chief urologic complaint was recorded and used to initially characterize the bladder storage or voiding symptoms. Patient evaluation included history and physical examination, urinalysis, post void bladder ultrasound, and urodynamic studies. Successful treatment modalities that subjectively or objectively improved symptoms were recorded. RESULTS: Of 815 patients with the diagnosis of dysautonomia, 82 (10 %) were referred for evaluation of lower urinary tract dysfunction. Mean age was 47 years (range 12-83) and 84 % were female. The chief complaint was urinary urgency ± incontinence in 61 % and hesitancy in 23 % of patients. Urodynamic findings demonstrated detrusor overactivity ± incontinence in 50 % of patients, although chief complaint did not reliably predict objective findings. Successful objective and subjective treatments were multimodal and typically non-operative. INTERPRETATION: Lower urinary tract dysfunction may develop in at least 10 % of patients with dysautonomia, predominantly females. Bladder storage or voiding complaints do not reliably predict urodynamic findings. Urodynamically, most patients exhibited detrusor overactivity. The majority of patients were successfully managed with medical or physical therapy.

Dysautonomia is frequent in Machado-Joseph disease: clinical and neurophysiological evaluation.

Autonomic dysfunction has been already described in patients with SCA3/MJD, but several important questions remain unanswered. The objectives of this study are to determine the frequency and the intensity of autonomic manifestations in SCA3/MJD, as well as to identify possible correlations between autonomic manifestations and genetic and clinical parameters. We have performed clinical and electrophysiological evaluations of 40 patients with SCA3/MJD and 38 healthy controls. We used the Scale for the Assessment and Rating of Ataxia (SARA) and the scales for Outcomes in Parkinson's Disease: Autonomic Questionnaire to quantify the severity of ataxia and autonomic complaints, respectively. We also studied heart rate variability at rest, during orthostatic challenge (30:15 ratio), Valsalva maneuver (Valsalva index), and deep breathing (E/I ratio). We evaluated spectral analyses of RR intervals at rest and the sympathetic skin response. Mean RR intervals at rest and the 30:15 ratio were different between patients and controls (811.8 versus 933.4 ms; p = 0.001 and 1.10 versus 1.15; p = 0.038, respectively). The Valsalva index and the E/I ratio were similar between the groups (p = 0.373 and p = 0.08). Spectral analysis presented distinct results in patients and controls, related to low- and high-frequency power (p < 0.001 and <0.001, respectively). We found cardiovascular and sympathetic sweat disautonomia in 30 % and 45 % of the patients with SCA3/MJD. Autonomic manifestations were related neither to genetic (CAG repeat length) nor clinical parameters (age, disease duration, SARA scores). Autonomic dysfunction is frequent and sometimes disabling in SCA3/MJD. We found evidence of both cardiovascular and sudomotor dysfunction in the disease.

Nutritional risk and gastrointestinal dysautonomia symptoms in Parkinson's disease outpatients hospitalised on a scheduled basis.

Dysautonomia symptoms of nutritional interest may often occur in Parkinson's disease (PD), but the role played in affecting the risk of malnutrition still needs to be clarified. A total of 208 consecutive PD outpatients hospitalised on a scheduled basis were assessed for nutritional risk by the Malnutrition Universal Screening Tool. Presence of dysautonomia symptoms (dysphagia, sialorrhoea and constipation) was investigated using clinical rating scales. In our population, prevalence of nutritional risk was 17·2 (95 % CI 12·1, 24·0) % and relied mainly on unintentional weight loss. Sialorrhoea, dysphagia, dysphagia to liquids and constipation were observed in 10·6, 11·0, 14·4 and 59·6 % of the patients, respectively. Nutritional risk was independently associated with the number of dysautonomia symptoms (OR 1·39 (95 % CI 1·00, 1·96); P= 0·048) but not with single symptoms. An independent association was also found with the severity of motor symptoms (Hoehn-Yahr stage, OR 1·48 (95 % CI 1·00, 2·55); P= 0·049) and levodopa dose (OR 1·16 (95 % CI 1·04, 1·31) mg/kg per d; P= 0·009). Nutritional risk in PD outpatients appears to depend mainly on dysautonomic syndrome, disease severity and levodopa dosage. Implications for outcome deserve further investigation. The assessment of nutritional status and of gastrointestinal dysautonomia symptoms should be part of the routine work-up of a PD patient.

Prevalence and patterns of symptoms of dysautonomia in patients with long-COVID syndrome: A cross-sectional study.

BACKGROUND: The association between autonomic dysfunction and long-COVID syndrome is established. However, the prevalence and patterns of symptoms of dysautonomia in long-COVID syndrome in a large population are lacking. OBJECTIVE: To evaluate the prevalence and patterns of symptoms of dysautonomia in patients with long-COVID syndrome. METHODS: We administered the Composite Autonomic Symptom Score 31 (COMPASS-31) questionnaire to a sample of post-COVID-19 patients who were referred to post-COVID clinic in Assiut University Hospitals, Egypt for symptoms concerning for long-COVID syndrome. Participants were asked to complete the COMPASS-31 questionnaire referring to the period of more than 4 weeks after acute COVID-19. RESULTS: We included 320 patients (35.92 ± 11.92 years, 73% females). The median COMPASS-31 score was 26.29 (0-76.73). The most affected domains of dysautonomia were gastrointestinal, secretomotor, and orthostatic intolerance with 91.6%, 76.4%, and 73.6%, respectively. There was a positive correlation between COMPASS-31 score and long-COVID duration (p < 0.001) and a positive correlation between orthostatic intolerance domain score and post-COVID duration (p < 0.001). There was a positive correlation between orthostatic intolerance domain score and age of participants (p = 0.004). Two hundred forty-seven patients (76.7%) had a high score of COMPASS-31 >16.4. Patients with COMPASS-31 >16.4 had a longer duration of long-COVID syndrome than those with score <16.4 (46.2 vs. 26.8 weeks, p < 0.001). CONCLUSIONS: Symptoms of dysautonomia are common in long-COVID syndrome. The most common COMPASS-31 affected domains of dysautonomia are gastrointestinal, secretomotor, and orthostatic intolerance. There is a positive correlation between orthostatic intolerance domain score and patients' age.

Risk factors related to dysautonomia after severe traumatic brain injury.

BACKGROUND: Dysautonomia after severe traumatic brain injury (TBI) is a clinical syndrome affecting a subgroup of survivors and is characterized by episodes of autonomic dysregulation and muscle overactivity. The purpose of this study was to determine the incidence of dysautonomia after severe TBI in an intensive care unit setting and analyze the risk factors for developing dysautonomia. METHODS: A consecutive series of 101 patients with severe TBI admitted in a major trauma hospital during a 2-year period were prospectively observed to determine the effects of age, sex, mode of injury, hypertension history, admission systolic blood pressure, fracture, lung injury, admission Glasgow Coma Scale (GCS) score, injury severity score, emergency craniotomy, sedation or analgesia, diffuse axonal injury (DAI), magnetic resonance imaging (MRI) scales, and hydrocephalus on the development of dysautonomia. Risk factors for dysautonomia were evaluated by using logistic regression analysis. RESULTS: Seventy-nine of the 101 patients met inclusion criteria, and dysautonomia was observed in 16 (20.3%) of these patients. Univariate analysis revealed significant correlations between the occurrence of dysautonomia and patient age, admission GCS score, DAI, MRI scales, and hydrocephalus. Sex, mode of injury, hypertension history, admission systolic blood pressure, fracture, lung injury, injury severity score, sedation or analgesia, and emergency craniotomy did not influence the development of dysautonomia. Multivariate logistic regression revealed that patient age and DAI were two independent predictors of dysautonomia. There was no independent association between dysautonomia and admission GCS score, MRI scales, or hydrocephalus. CONCLUSIONS: Dysautonomia frequently occurs in patients with severe TBI. A younger age and DAI could be risk factors for facilitating the development of dysautonomia.

Diffuse axonal injury in patients with head injuries: an epidemiologic and prognosis study of 124 cases.

BACKGROUND: Diffuse axonal injury (DAI) is usually associated to severe trauma. Recent imaging advances made its diagnosis easier. Its prognosis impact is not yet well established. The aim of this article is to describe the epidemiologic, clinical, and radiologic features of posttraumatic DAI and to study its prognosis impact on mortality and outcome according to Glasgow Outcome Scale. METHODS: This is a retrospective study over a 4-year period (2004-2007) of 124 patients admitted for head trauma. Demographic, clinical, biological, and radiologic findings were recorded at admission and during intensive care unit stay. RESULTS: Mean age (±standard deviation) was 28 years±15.8 years. Cranial computed tomography scan was sufficient enough to diagnose DAI in 31 patients. Magnetic resonance imaging was performed in 105 patients with a delay of 7.7 days±8.6 days. Most patients were classified as stage II (49.5%) or stage III (44.8%) according to Gentry's classification. In a multivariate analysis, factors associated with higher mortality were dysautonomia (p=0.018; odds ratio [OR]=4.17), hyperglycemia≥8 mmol/L (p=0.001; OR=3.84) on intensive care unit admission, and subdural hematoma (p=0.031; OR=3.99), whereas factors associated to poor outcome according to Glasgow Outcome Scale score were Glasgow Coma Scale score<8 (p=0.032, OR=3.55), secondary systemic injuries score≥3 (p=0.034, OR=2.83), hyperglycemia≥8 mmol/L (p=0.002, OR=5.55), and DAI count≥6 (p=0.035, OR=3.33). In patients with pure DAI, the absence of consciousness recovery was the unique independent factor of mortality (p<0.001, OR=116.4), whereas only transfusion need was an independent factor of poor outcome (p=0.017, OR=4.44). CONCLUSION: Dysautonomia, hyperglycemia, and subdural hematoma are the main factors associated to higher mortality when DAIs are diagnosed, whereas a DAI count≥6 is associated to poor outcome. Magnetic resonance imaging classification did not have a prognosis value even in patients with pure DAI.

Paroxysmal sympathetic hyperactivity after acquired brain injury: a review of diagnostic criteria.

PRIMARY OBJECTIVE: To evaluate the development and usage of diagnostic criteria for paroxysmal sympathetic hyperactivity (PSH) following acquired brain injury (ABI), then comparatively analyse published criteria. RESEARCH DESIGN: Systematic literature review. METHODS AND PROCEDURES: Literature published in English language prior to 30 November 2008 was reviewed for dysautonomic syndromes following ABI, characterized by simultaneous paroxysmal autonomic hyperactivity and motor over-activity. MAIN OUTCOME AND RESULTS: Sixty papers presenting 349 cases of PSH were identified, with a further 21 papers providing additional information regarding the condition. Only 27 of these 81 papers (33%) utilized diagnostic criteria. There were nine novel or substantially modified diagnostic criteria sets, which were analysed further. Criteria showed strong agreement on core clinical features of PSH-heart rate (HR), blood pressure, respiratory rate, temperature, sweating, and motor hyperactivity. Most criteria sets utilized a polythetic diagnostic system and all but one indicated severity thresholds, e.g. HR >120 beats per minute. Two papers specified a minimum episode frequency and four papers required a minimum syndrome duration. CONCLUSIONS: Of necessity, diagnostic criteria have been developed ad hoc. The differences between criteria complicate both clinical diagnosis and the process of comparing research cohorts. These findings demarcate the need for a single set of PSH diagnostic criteria and provide the substrate for scientific consensus.