Mitchell G. Miglis

Intracranial Venous Thrombosis After Placement of a Lumbar Drain

BackgroundLumbar drains are frequently used in clinical neuroscience and are often managed in the neurointensive care unit. Complications are generally rare, and intracranial venous thrombosis (IVT) and infarction has not been reported.MethodsWe report the case of a 45-year-old woman who developed a cerebrospinal fluid (CSF) leak after spinal surgery. Fifteen hours after placement of a lumbar drain she developed pure alexia and color agnosia caused by left lateral sinus thrombosis with hemorrhagic infarction in the posterior inferior left temporal lobe. We review the literature on the association of IVT with injury to the spinal dura, and we propose a mechanism whereby the lumbar drain may facilitate its development.ResultsWe found 29 cases in which spinal dural injury was followed by IVT. The association is not coincidental, because nearly all cases were associated with post-dural puncture headache, which occurs in only a minority of cases of dural puncture. Injury to the spinal dura alters the distribution of craniospinal elasticity causing profound intracranial CSF hypotension on assuming the erect posture. This causes acute dilation of cerebral veins resulting in both orthostatic headache and venous stasis. We propose that placement of the lumbar drain and elevation of the head of the bed aggravated intracranial CSF hypotension and facilitated IVT.ConclusionsWhen a lumbar drain is placed for treatment of a spinal CSF leak, the patient should remain flat in bed. Any patient with post-dural injury headache that intensifies after an initial plateau, persists for longer than a week, or loses its orthostatic character should be evaluated for intracranial sinus or venous thrombosis.

Kleine-Levin syndrome: a review

Kleine-Levin syndrome is a recurrent hypersomnia associated with symptoms of hyperphagia, hypersexuality, and cognitive impairment. This article reviews the current available research and describes common clinical symptoms, differential diagnosis, and acceptable workup and treatment. Although deficits have traditionally been thought to resolve between episodes, functional imaging studies and long-term neuropsychological testing in select patients have recently challenged this notion. This may suggest that Kleine-Levin syndrome is not as benign as previously considered.

Effect of taurine on platelets and the plasma coagulation system.

It is not yet clear what exact mechanisms are at work in hibernating animals that prevent clot formation and maintain tissue perfusion under conditions of very slow blood flow and increased blood viscosity brought about by the low temperatures. It has been shown that the total amino acid pool increases more then two fold in hibernating animals with taurine accounting for about 50% of this increase [Storey et al ., Proc Natl Acad Sci USA 1988; 85(21): 8350-4]. This work investigates the effect of taurine on platelets and the plasma coagulation system. Taurine was added at different concentrations in the range between 5 and 25 mM to donor plasma. Using STA/STA Compact coagulation analyzer the following tests were performed: prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT). At the highest concentration tested (25 mM) taurine prolonged TT by 9%. The prolongation was statistically significant but not clinically significant retaining TT within normal limits (16.7-20.7 s). PT and APTT remained unchanged by taurine. The effect of taurine on platelets was assessed by platelet aggregation by thrombin, extent of platelet shape change (ESC) induced by ADP, and thrombelastography. Taurine at 5 mM final concentration inhibited platelet aggregation by 10%. Increasing taurine concentration to 25 mM did not result in a further augmentation of the inhibitory effect. ESC was unaffected by taurine. Clot strength determined by thrombelastography also remained unchanged by taurine.

Autonomic dysfunction in primary sleep disorders

The autonomic nervous system plays an important role in the coordination of many important physiologic functions during sleep. Many patients with untreated sleep disorders will describe symptoms of autonomic impairment, and a majority of patients with autonomic impairment have some form of sleep disorder. This article will explore possible explanations for this connection, as well as review the current literature on autonomic impairment in common primary sleep disorders including obstructive sleep apnea, insomnia, restless legs syndrome, periodic limb movement disorder, narcolepsy, and rapid eye movement sleep behavior disorder.

Migraine and Autonomic Dysfunction: Which Is the Horse and Which Is the Jockey?

Purpose of ReviewSymptoms of autonomic dysfunction are common in patients with migraine, both during and between migraine attacks. Studies evaluating objective autonomic testing in patients have found significant, though somewhat conflicting results. The purposes of this review are to summarize and interpret the key findings of these studies, including those evaluating heart rate variability, autonomic reflex testing, and functional imaging in patients with migraine. The neuroanatomy of the central autonomic network as it relates to migraine is also reviewed.Recent FindingsSeveral studies have evaluated autonomic balance in migraineurs, with conflicting results on the magnitude of sympathetic versus parasympathetic dysfunction. Most studies demonstrate sympathetic impairment, with a lesser degree of parasympathetic impairment.SummaryThree trends have emerged: (1) migraine with aura tends to produce more significant autonomic dysfunction than migraine without aura, (2) sympathetic impairment is more common than parasympathetic impairment, and (3) sympathetic impairment is common in the interictal period, with increased sympathetic responsiveness during the ictal period, suggesting adrenoreceptor hypersensitivity.

Is pure autonomic failure an early marker for Parkinson disease, dementia with Lewy bodies, and multiple system atrophy? And other updates on recent autonomic research

Pure autonomic failure (PAF) is a disorder of a-synuclein deposition that results in neurogenic orthostatic hypotension (OH) and other features of autonomic failure, without signs of central nervous system (CNS) involvement. If patients are followed for a sufficient period, some may eventually develop Parkinson disease (PD), multiple system atrophy (MSA), or dementia with Lewy bodies (DLB). Determining which patients will go on to convert to a CNS synucleinopathy and which will remain as PAF has been, so far, a prognostic dilemma for medical providers. Is PAF purely peripheral and restricted to the autonomic nerves, or does it presage a more widespread CNS disorder? A recent pivotal paper published in the Annals of Neurology by members of the U.S. Autonomic Disorders Consortium reports the results of the natural history of pure autonomic failure, enrolling patients with PAF and followed annually for a 4-year period [3]. All subjects underwent extensive clinical and autonomic testing, including cognitive screening, olfaction, and supine, and upright serum norepinephrine levels. This multi-center study performed at five U.S. sites enrolled 75 patients with PAF, the largest cohort reported to date. The majority of them were male (70%), and the mean duration of disease since onset of autonomic symptoms was 5 years. Ninety-five percent of patients reported orthostatic intolerance, 58% constipation, 50% urinary symptoms, 44% abnormalities of sweating, and 65% of men reported erectile dysfunction. All patients had evidence of OH on tilt testing, and all patients had an absent phase IV overshoot on Valsalva maneuver, indicative of neurogenic OH (nOH). Seventy-one percent had reduced heart rate variability with deep breathing and 54% had reduced serum norepinephrine levels on upright tilt. The prevalence of probable rapid eye movement (REM) sleep behavior disorder (RBD) by questionnaires was 72%, raising the possibility of brainstem involvement. Interestingly, a similar prevalence of polysomnography-confirmed RBD (63%) was documented in a small cohort of PAF patients [4]. Olfactory function was significantly impaired in 73% of the natural history cohort, further indicating CNS involvement. At 1-year follow up, 15% of patients converted to a CNS synucleinopathy (two PD, four DLB, and five MSA). The conversion rates of the remaining patients at years two, three, and four were 13, 13, and 27%, respectively. Predictors of phenoconversion to PD/DLB included impaired olfactory function with probable RBD, and phenoconverstion to MSA included preserved olfaction with probable RBD. Subtle motor deficits were noted in 88% of patients that converted to a CNS synucleinopathy. This study supports the notion that a-synuclein spreads in a prion-like fashion through adjacent cells. However, not all patients with a PAF phenotype may be associated with a-synuclein spread, as described in a case-report in this issue of Clinical Autonomic Research [2]. The Natural History Study of Synucleinopathies continues on its second iteration, as a multi-center, National Institutes of Health (NIH)-sponsored study hoping to expand these results. Several sites in North America, South America, Europe, and Asia participating in this study are currently enrolling patients with PAF, MSA and idiopathic RBD in order to document the natural history of these & Srikanth Muppidi muppidis@stanford.edu

Kleine-Levin Syndrome

Kleine-Levin syndrome is a rare recurrent hypersomnia associated with symptoms of behavioral and cognitive impairment. This article reviews common presenting symptoms, differential diagnosis, diagnostic workup, and potential treatment options. Current updates on functional imaging studies and long-term neuropsychological studies are reviewed.

Seropositive myasthenia and autoimmune autonomic ganglionopathy: Cross reactivity or subclinical disease?

Autoimmune autonomic ganglionopathy (AAG) and myasthenia gravis (MG) are both autoimmune channelopathies mediated by antibodies directed against nicotinic acetylcholine receptors. While both diseases target acetylcholine receptors, skeletal muscle and ganglionic receptor subtypes have key immunologic and genetic distinctions, and reports of patients with both AAG and MG are rare. We report a patient with antibody-confirmed AAG and elevated levels of ACh binding antibodies that did not meet clinical or electrodiagnostic criteria for MG. We presume that his skeletal muscle nAChR seropositivity was a false positive, perhaps due to the cross reactivity of the patients ganglionic nAChR antibodies with skeletal nAChR subtypes.

Autonomic dysfunction predicts poor outcome in stroke: Updates on recent autonomic research

Inpatient neurologists are well aware of how common autonomic dysfunction is in patients with acute stroke. For those of us who no longer practice inpatient medicine, we can still remember the many stroke patients we cared for during our neurology training: labile blood pressures, refractory hypertension, fevers, and cardiac arrhythmias were not uncommon, despite aggressive treatments. Research has demonstrated that impaired heart rate variability correlates with both post-stroke disability [4] and all-cause mortality [5]. What is less clear is the how the magnitude of autonomic dysfunction in the acute stroke period influences stroke recovery. Xiong and colleagues have attempted to help answer this question in their recent paper published in the December 4, 2017 issue of Stroke [6]. The authors recruited 150 adult patients who were admitted for mild acute ischemic stroke (NIHSS 4–10). Stroke was confirmed on imaging, and patients were recruited within 7 days of stroke symptom onset. Patients with arrhythmias such as atrial fibrillation were excluded, as were those with hemodynamic instability or major concurrent illness (ex. chronic obstructive pulmonary disease, renal failure, active malignancy), as these variables may have altered autonomic testing results. Autonomic cardiovascular testing was performed with a portable system (Task Force Monitoring, CNSystems) capable of measuring beat-to-beat BP and HR. All patients underwent measures of HR variability with deep breathing, Valsalva maneuver, sustained handgrip testing, and active standing to calculate BP responses and the 30:15 ratio. Patients were grouped according to the Ewing classification [7]: Normal: all tests normal or one borderline; early involvement: one of the three HR tests abnormal or two borderline; definite involvement: two or more of the HR tests abnormal; severe involvement: two or more of the HR tests abnormal plus one or both of the BP pressure tests abnormal, or both borderline; atypical pattern: any other combination of abnormal tests. Patients with normal or early impairment were classified as “minor autonomic function impairment” by the authors, whereas the remaining patients in the definite, severe, or atypical groups were classified as “significant autonomic function impairment.” Patients were reassessed at 3 months, and their outcome was dichotomized based on their Rankin score: good (modified Rankin Scale score 0–2) or poor (modified Rankin Scale score 3–6). The authors then calculated odds ratios of the magnitude of autonomic dysfunction related to poor functional outcome. Most patients were men (71%), with a mean age of 66.4 ± 9.9 years. The majority (76.0%) of patients were classified as having significant autonomic dysfunction. After adjusting for statistically significant confounding variables, such as gender and NIHSS on admission, the magnitude of autonomic dysfunction independently predicted an unfavorable outcome, with an odds ratio of 3.263 (95% confidence interval, 1.141–9.335; p = 0.027). A poor functional outcome was seen in 32.5% of patients with significant autonomic impairment, compared to 13.9% of patients with minor autonomic impairment (p = 0.031). Patients in the poor outcome group were more likely to be women, have a higher NIHSS score on admission, and have more significant autonomic dysfunction. The authors suggest several possible explanations for the greater risk of poor outcome in those with significant * Srikanth Muppidi muppidis@stanford.edu

Postural tachycardia in hypermobile Ehlers-Danlos syndrome: A distinct subtype?

INTRODUCTION It is not clear if patients with postural tachycardia syndrome (POTS) and Ehlers-Danlos syndrome (hEDS) differ from patients with POTS due to other etiologies. We compared the results of autonomic testing and healthcare utilization in POTS patients with and without hEDS. METHODS Patients with POTS+hEDS (n=20) and POTS controls without hypermobility (n=20) were included in the study. All patients underwent autonomic testing, and the electronic medical records were reviewed to determine the number and types of medications patients were taking, as well as the number of outpatient, emergency department, and inpatient visits over the prior year. RESULTS Patients with hEDS had twice as many outpatient visits (21 v. 10, p=0.012), were taking more prescription medications (8 vs. 5.5, p=0.030), and were more likely to see a pain physician (70% vs 25%, p=0.005). Autonomic testing demonstrated a slight reduction in heart rate variability and slightly lower blood pressures on tilt table testing in hEDS patients, however for most patients these variables remained within the range of normal. Orthostatic tachycardia on tilt table testing was greater in POTS controls (46bpm vs 39bpm, p=0.018). Abnormal QSweat responses were common in both groups (38% of POTS+hEDS and 36% of POTS controls). CONCLUSIONS While autonomic testing results were not significantly different between groups, patients with POTS+hEDS took more medications and had greater markers of healthcare utilization, with chronic pain likely playing a prominent role.