A case series of REM sleep behavior disorder in pure autonomic failure.

PURPOSE: Data on the prevalence of RBD in patients with PAF are limited, with discrepancies in the literature regarding prevalence. We aimed to provide further data on this association with a series of eight patients with PAF. METHODS: We reviewed the electronic medical records of all patients seen at the Stanford neurology clinics from 2012 to 2016 who were given a provisional diagnosis of PAF (343 patients), and further screened by procedure codes to identify those patients who underwent both attended video-polysomonography and autonomic testing (18 patients), and met strict exclusionary criteria (8 patients). RESULTS: The mean age of our patients was 69 years, and 63 % were women. The mean duration of autonomic symptoms was 11.2 years, and the mean duration of dream enactment was 3.75 years. All patients demonstrated evidence of adrenergic failure on autonomic testing. Five out of 8 (63 %) met diagnostic criteria for RBD, confirmed on vPSG. CONCLUSIONS: Our series supports the concept that RBD in PAF may be more common than previously reported, and that the presence of RBD suggests brainstem involvement in some cases of PAF. In addition, the timing of RBD symptoms relative to the emergence of autonomic symptoms may be useful to help distinguish these conditions.

Sleep disorders in patients with postural tachycardia syndrome.

OBJECTIVE: Patients with postural tachycardia syndrome (POTS) often describe symptoms of fatigue, sleepiness, and lack of refreshing sleep. We aimed to provide further objective measures of sleep in patients with POTS. METHODS: POTS patients (n = 18) were selected based on autonomic testing and evaluation at our center. Controls (n = 16) of similar age, gender, and BMI were selected from new patients referred to the Stanford Sleep Disorders Clinic for any sleep-related complaint. All patients underwent polysomnography and completed several sleep questionnaires and a 2-week sleep diary. RESULTS: POTS patients and control subjects were of similar age (27 ± 10.2 vs. 29 ± 5.4 years, p = 0.92) and Body Mass Index (21 ± 3.8 vs. 24 ± 4.1, p = 0.14). The majority of subjects in both groups were females (72 % POTS vs. 81 % controls). POTS patients scored higher on subjective fatigue scales but not sleepiness scales. POTS patients scored in the normal range on the BDI and the "evening" category on the MEQ. Their sleep diaries were not different from controls. With the exception of mild OSA, slightly reduced %REM and prolonged REM latency, their PSG data were normal and no different from controls. CONCLUSIONS: It is unlikely that the sleep-related complaints of POTS patients are the result of a primary sleep disorder unique to POTS. We propose that a combination of factors such as body fatigue, chronic pain, and other somatic symptoms common in POTS patients might be the underlying reason for sleep-related symptoms in POTS.

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.

Prevalence of REM sleep behavior disorder in multiple system atrophy: a multicenter study and meta-analysis.

OBJECTIVE: Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia frequently affecting patients with synucleinopathies, but its exact prevalence in multiple system atrophy (MSA) is unclear. Whether questionnaires alone are sufficient to diagnose RBD is also unknown. METHODS: We performed a cross-sectional study of patients with probable MSA from six academic centers in the US and Europe. RBD was ascertained clinically and with polysomnography; we also performed a meta-analysis according to PRISMA guidelines for studies published before September 2014 that reported the prevalence of RBD in MSA. A random-effects model was constructed using weighted prevalence proportions. Only articles in English were included. Studies were classified into those that ascertained the presence of RBD in MSA clinically and with polysomnography. Case reports or case series (≤ 5 patients) were not included. RESULTS: Forty-two patients completed questionnaires and underwent polysomnography. Of those, 32 (76.1%) had clinically suspected RBD and 34 (81%) had polysomnography-confirmed RBD. Two patients reported no symptoms of RBD but had polysomnography-confirmed RBD. The primary search strategy yielded 374 articles of which 12 met the inclusion criteria. The summary prevalence of clinically suspected RBD was 73% (95 % CI, 62-84%) in a combined sample of 324 MSA patients. The summary prevalence of polysomnography-confirmed RBD was 88 % (95% CI, 79-94%) in a combined sample of 217 MSA patients. INTERPRETATION: Polysomnography-confirmed RBD is present in up to 88% of patients with MSA. RBD was present in some patients that reported no symptoms. More than half of MSA patients report symptoms of RBD before the onset of motor deficits.

Cumulative Brain Injury from Motor Vehicle-Induced Whole-Body Vibration and Prevention by Human Apolipoprotein A-I Molecule Mimetic (4F) Peptide (an Apo A-I Mimetic).

BACKGROUND: Insidious cumulative brain injury from motor vehicle-induced whole-body vibration (MV-WBV) has not yet been studied. The objective of the present study is to validate whether whole-body vibration for long periods causes cumulative brain injury and impairment of the cerebral function. We also explored a preventive method for MV-WBV injury. METHODS: A study simulating whole-body vibration was conducted in 72 male Sprague-Dawley rats divided into 9 groups (N = 8): (1) 2-week normal control; (2) 2-week sham control (in the tube without vibration); (3) 2-week vibration (exposed to whole-body vibration at 30 Hz and .5 G acceleration for 4 hours/day, 5 days/week for 2 weeks; vibration parameters in the present study are similar to the most common driving conditions); (4) 4-week sham control; (5) 4-week vibration; (6) 4-week vibration with human apolipoprotein A-I molecule mimetic (4F)-preconditioning; (7) 8-week sham control; (8) 8-week vibration; and (9) 8-week 4F-preconditioning group. All the rats were evaluated by behavioral, physiological, and histological studies of the brain. RESULTS: Brain injury from vibration is a cumulative process starting with cerebral vasoconstriction, squeezing of the endothelial cells, increased free radicals, decreased nitric oxide, insufficient blood supply to the brain, and repeated reperfusion injury to brain neurons. In the 8-week vibration group, which indicated chronic brain edema, shrunken neuron numbers increased and whole neurons atrophied, which strongly correlated with neural functional impairment. There was no prominent brain neuronal injury in the 4F groups. CONCLUSIONS: The present study demonstrated cumulative brain injury from MV-WBV and validated the preventive effects of 4F preconditioning.

Wilms tumor presenting with Lambert-Eaton myasthenic syndrome.

Paraneoplastic syndromes may affect the central and peripheral nervous system of adults and children with cancer. Neurological symptoms may resolve with treatment of the underlying neoplasm. We report the case of a child with Wilms tumor who presented with generalized weakness, fatigue, ptosis, hypokinesis, dysarthria, urinary retention, facial diplegia, ophthalmoplegia, and autonomic dysfunction. Routine electrodiagnostic testing, including repetitive nerve stimulation, was normal. Clinical features and stimulation single-fiber electromyogram were consistent with a neuromuscular junction transmission disorder, likely Lambert-Eaton myasthenic syndrome. The child's neurological status returned to normal with successful treatment of the tumor.

Botulinum toxin injection for the treatment of upper esophageal sphincter dysfunction.

OBJECTIVES: We sought to review the dysphagia-related outcomes and quality of life in a series of patients with upper esophageal sphincter (UES) dysfunction treated with cricopharyngeal (CP) botulinum toxin (BTX) injection, and to identify patient characteristics or CP muscle histologic features that predict efficacy of BTX injection. METHODS: A retrospective chart review was performed on patients with UES dysfunction who underwent CP BTX injection. Dysphagia-related quality-of-life questionnaires based on the Eating Assessment Tool (EAT-10) were mailed to patients. RESULTS: Forty-nine patients (30 female, 19 male; average age, 59 +/- 16 years) with UES dysfunction have been treated at our institution with CP BTX injection since 2000. Seventeen of these patients also underwent CP myotomy. Injections of BTX were occasionally repeated after the treatment effect subsided, and the BTX dose varied widely (average, 39 +/- 19 units). Improvement in symptoms was noted by 65% of patients. The overall complication rate was minimal, although many patients complained of transient worsening of dysphagia after CP BTX injection. Biopsy specimens of the CP muscle were evaluated in the subset of patients with CP BTX injection who proceeded to myotomy, with results of neuropathic, myopathic, and mixed histologic subtypes. The EAT-10 scores demonstrated a general trend toward improved swallowing outcomes after CP BTX injection. CONCLUSIONS: This study reviewed findings from the largest published series of BTX treatment of UES dysfunction and evaluated the efficacy, patient satisfaction, and complications of this procedure. Dysphagia-related quality-of-life outcomes appear to be improved after CP BTX injection.

The correlation between calcium intensity and histopathological changes in brachial plexus nerve injuries.

BACKGROUND: After nerve injury, an influx of calcium exceeds the homeostatic capacity, which damages peripheral nerves. Previous studies identified that following nerve crush, function improves as calcium levels normalize. METHODS: Electrophysiological analysis was performed to measure the compound muscle action potential of 15 patients' damaged nerves. These samples were evaluated for calcium level and also stained with a Luxol fast blue and neurofilament antibodies to evaluate the myelin sheath and neurofilaments of the nerves. Based on the Sunderland scale, we identified three exclusive types of peripheral nerve injury groups. RESULTS: There was a correlation between histopathological damage and calcium levels of 0.81 (p < 0.005). The average relative fluorescence units (RFUs) was 235.28 ± 19, which corresponds to 5.3 × 10⁻7 M of calcium, five times the normal value. CONCLUSION: Our study shows promising clinical implications via faster pathology results by the RFU technique. This approach of calcium staining, though still in clinical trials, offers significant clinical application, allowing physicians to get the clinically diagnostic nerve injury degree faster and will also facilitate better strategies for further treatment or future surgeries.

Epileptic Seizure Induced by Head-Up Tilt: A Case Series Study.

PURPOSE: Epilepsy and syncope can be difficult to distinguish, with misdiagnosis resulting in unnecessary or incorrect treatment and disability. Combined tilt-table and video EEG (vEEG) testing (tilt-vEEG) is infrequently used to parse these entities even at large centers. Because of the discovery of a rare case of epileptic seizure induced by head-up tilt (HUT) (no prior cases have been published), the authors sought to verify the rarity of this phenomenon. METHODS: An observational, retrospective case series study of all combined tilt-vEEG studies performed at Stanford Health Care over a 2-year period was performed. Studies were grouped into categories: (1) abnormal tilt and normal vEEG; (2) abnormal vEEG and normal tilt; (3) abnormal vEEG and abnormal tilt; (4) normal tilt and normal vEEG, with neurologic symptoms; and (5) normal tilt and normal vEEG without neurologic symptoms. RESULTS: Sixty-eight percent of patients had an abnormal study (categories A-C), with only 3% having both an abnormal tilt and an abnormal EEG (category C). Of these, one patient had a focal epileptic seizure induced by HUT. With HUT positioning, the patient stopped answering questions and vEEG showed a left temporal seizure; systolic blood pressure abruptly dropped to 89 mm Hg (64 mm Hg below baseline); heart rate did not change, but pacemaker showed increased firing (threshold: <60 bpm). CONCLUSIONS: Combined tilt-table and vEEG evaluation was able to identify a previously unreported scenario-head-up tilt provocation of an epileptic seizure-and improve treatment. Combined tilt and vEEG testing should be considered for episodes that persist despite treatment to confirm proper diagnosis.

Stellate ganglion block catheter for paroxysmal sympathetic hyperactivity: calming the 'neuro-storm'.

BACKGROUND: Paroxysmal sympathetic hyperactivity (PSH) is an autonomic disorder affecting patients with severe acquired brain injury characterized by intermittent sympathetic discharges with limited therapeutic options. We hypothesized that the PSH pathophysiology could be interrupted via stellate ganglion blockade (SGB). CASE PRESENTATION: A patient with PSH after midbrain hemorrhage followed by hydrocephalus obtained near-complete resolution of sympathetic events for 140 days after SGB. CONCLUSION: SGB is a promising therapy for PSH, overcoming the limitations of systemic medications and may serve to recalibrate aberrant autonomic states.

Differential Findings on Anorectal Manometry in Patients with Parkinson's Disease and Defecatory Dysfunction.

Introduction: Gastrointestinal dysfunction, particularly constipation, is among the most common non-motor manifestations in Parkinson's Disease (PD). We aimed to identify high-resolution anorectal manometry (HR-ARM) abnormalities in patients with PD using the London Classification. Methods: We conducted a retrospective review of all PD patients at our institution who underwent HR-ARM and balloon expulsion test (BET) for evaluation of constipation between 2015 and 2021. Using age and sex-specific normal values, HR-ARM recordings were re-analyzed and abnormalities were reported using the London Classification. A combination of Wilcoxon rank sum and Fisher's exact test were used. Results: 36 patients (19 women) with median age 71 (interquartile range [IQR]: 69-74) years, were included. Using the London Classification, 7 (19%) patients had anal hypotension, 17 (47%) had anal hypocontractility, and 3 women had combined hypotension and hypocontractility. Anal hypocontractility was significantly more common in women compared to men. Abnormal BET and dyssynergia were noted in 22 (61%) patients, while abnormal BET and poor propulsion were only seen in 2 (5%). Men had significantly more paradoxical anal contraction and higher residual anal pressures during simulated defecation, resulting in more negative recto-anal pressure gradients. Rectal hyposensitivity was seen in nearly one third of PD patients and comparable among men and women. Conclusion: Our data affirms the high prevalence of anorectal disorders in PD. Using the London Classification, abnormal expulsion and dyssynergia and anal hypocontractility were the most common findings in PD. Whether the high prevalence of anal hypocontractility in females is directly related to PD or other confounding factors will require further research.

Children With PANS May Manifest POTS.

Objectives: Pediatric acute-onset neuropsychiatric syndrome (PANS) is characterized by an abrupt-onset of severe psychiatric symptoms including OCD, anxiety, cognitive difficulties, and sleep issues which is thought to be a post-infection brain inflammatory disorder. We observed postural orthostatic tachycardia syndrome (POTS) which resolved with immunomodulation in a patient with Pediatric acute-onset neuropsychiatric syndrome (PANS). Here, we aim to present a case of POTS and to examine the prevalence of (POTS) in our PANS cohort, and compare the clinical characteristics of patients with and without POTS. Study Design: We conducted this cohort study of patients meeting PANS criteria who had at least three clinic visits during the study period. We included data from prospectively collected questionnaires and medical record review. We present a case followed by statistical comparisons within our cohort and a Kaplan-Meier analysis to determine the time-dependent risk of a POTS diagnosis. Results: Our study included 204 patients: mean age of PANS onset was 8.6 years, male sex (60%), non-Hispanic White (78%). Evidence of POTS was observed in 19/204 patients (9%) with 5/19 having persistent POTS defined as persistent abnormal orthostatic vitals, persistent POTS symptoms, and/or continued need for pharmacotherapy for POTS symptoms for at least 6 months). In this PANS cohort, patients with POTS were more likely to have comorbid joint hypermobility (63 vs 37%, p = 0.04), chronic fatigue (42 vs 18%, p = 0.03), and a family history of chronic fatigue, POTS, palpitations and syncope. An unadjusted logistic regression model showed that a PANS flare (abrupt neuropsychiatric deterioration) was significantly associated with an exacerbation of POTS symptoms (OR 3.3, 95% CI 1.4-7.6, p < 0.01). Conclusions: Our study describes a high prevalence of POTS in patients with PANS (compared to the general population) and supports an association between POTS presentation and PANS flare within our cohort.

Helicoid end-to-side and oblique attachment technique in repair of the musculocutaneous nerve injury with the phrenic nerve as a donor: an experimental study in rats.

The purpose of this study was to identify if a modified end-to-side repair can achieve equal results of nerve regeneration compared to an end-to-end repair using donor phrenic nerves in repair of the musculocutaneous nerve and also pulmonary protection. Eighteen rats were divided into three groups of six each comparing two nerve graft techniques: helicoid end-to-side plus distal oblique repair vs. traditional end-to-end repair, using a donor phrenic nerve. The saphenous nerve was used as a graft between the phrenic nerve and the musculocutaneous nerve. The third group was used as control; the musculocutaneous nerve was transected without any repair. Three months postoperatively, electrophysiology, tetanic force, moist muscle weight, histology, nerve fiber counting, and chest X-ray were evaluated. All results have shown that this modified end-to-side repair was superior to the end-to-end repair. The former did not compromise the diaphragm function, but the latter showed an elevation of the diaphragm. Little recovery was seen in the third group. The conclusion is that this modified end-to-side repair can replace the traditional end-to-end repair using donor phrenic nerves with better results of nerve regeneration without diaphragm compromise.

Myasthenia Symptom Burden, Fatigue, and Sleep: Are They Related?

OBJECTIVE: Our aim is to explore the relationship between myasthenia gravis (MG)-related symptom burden, sleep quality, and fatigue in a diverse group of self-identified MG patients. METHODS: Patients provided relevant myasthenia disease data and completed the MG QOL-15, Epworth sleepiness scale, Pittsburgh Sleep Quality Index, and fatigue severity score (FSS) online. MG activities of daily living scale (MG-ADL) was completed on a follow-up telephone interview. RESULTS: One hundred ninety-six patients completed the online survey and 99 provided MG-ADL data. The mean age was 52 ± 15.34 years, 88 were acetylcholine receptor antibody positive, and 21 were muscle specific kinase positive. The mean MG-ADL was 6.81, indicating a moderate MG disease burden. Forty-seven (24%) reported high Epworth sleepiness scale scores, 152 (77%) reported high Pittsburgh Sleep Quality Index scores, and 162 (82%) reported high FSS scores. Correlation analysis correcting for body mass index and sleep apnea revealed a moderate positive correlation between MGQOL-15, MG-ADL, and FSS. CONCLUSIONS: There is a moderate positive correlation between various MG-specific outcome measures and fatigue severity.

Cutaneous α-synuclein is correlated with autonomic impairment in isolated rapid eye movement sleep behavior disorder.

STUDY OBJECTIVES: To define the clinical implications of cutaneous phosphorylated α-synuclein (p-syn) and its association with subjective and objective measures of autonomic impairment and clinical features including antidepressant use in isolated rapid eye movement (REM) sleep behavior disorder (iRBD). METHODS: Twenty-five iRBD patients had quantified neurological and cognitive examinations, olfactory testing, questionnaires, autonomic function testing, and 3 punch skin biopsies (distal thigh, proximal thigh, neck). Skin biopsies were stained for the pan-axonal marker PGP 9.5 and co-stained with p-syn, and results were compared to 28 patients with Parkinson's disease (PD) and 18 healthy controls. Equal numbers of iRBD patients on and off antidepressants were recruited. The composite autonomic severity scale (CASS) was calculated for all patients. RESULTS: P-syn was detected in 16/25 (64%) of iRBD patients, compared to 27/28 (96%) of PD and 0/18 controls. The presence of p-syn at any biopsy site was correlated with both sympathetic (CASS adrenergic r = 0.6, p < 0.05) and total autonomic impairment (CASS total r = 0.6, p < 0.05) on autonomic reflex testing in iRBD patients. These results were independent of the density of p-syn at each site. There was no correlation between p-syn and antidepressant use. CONCLUSIONS: In patients with iRBD, the presence of cutaneous p-syn was detected in most patients and was associated with greater autonomic dysfunction on testing. Longitudinal follow-up will aid in defining the predictive role of both skin biopsy and autonomic testing in determining phenoconversion rates and future disease status.

Impact of autonomic dysfunction on inflammatory bowel disease.

UNLABELLED: Functional symptoms are common in patients with inflammatory bowel disease (IBD). The autonomic nervous system has been proposed to be involved in the pathogenesis of IBD. Autonomic dysfunction (AD) is associated with systemic manifestations and altered gut motility that may contributed to functional symptoms. AIM: To examine the impact of clinically manifest AD on patients with IBD. METHODS: This was a retrospective case-control study from a single tertiary referral IBD center. The cases comprised 43 IBD patients with AD diagnosed using a standardized battery of tests. Three disease-matched controls were selected for each case. We performed multivariate regression to compare health-related quality of life (SIBDQ), disease activity scores, and healthcare utilization. RESULTS: Female sex (83.7% vs. 53.5%, P<0.001) and psychiatric comorbidity (41.9% vs. 10.9%, P<0.001) were more common among IBD patients with AD than IBD controls. Small bowel transit times were significantly longer in cases (92.7 min) compared with controls (62.9 min, P=0.02). On multivariate analysis, AD was associated with a 7-point lower adjusted SIBDQ score compared with IBD controls [odds ratio (OR)-7.50; 95% confidence interval (CI), -12.0--3.03]. AD was also significantly associated with having more than 3 annual gastroenterology office visits (OR 2.84; 95% CI, 1.09-7.35), and 1 or more IBD-related medical hospitalizations (OR 2.49; 95% CI, 1.09-5.71). CONCLUSIONS: Clinically manifest AD is associated with lower quality of life and higher healthcare utilization in IBD patients. They may represent a cohort at risk for worse outcomes.