Thomas Chelimsky

Introduction: Acute ischemic stroke varies in presentation, and it is crucial to quickly identify patients presenting with stroke for timely intervention. Secondary movement disorders occurring after a delayed period following ischemic stroke have been well‐documented, though rare. Holmes tremor specifically has been described as a delayed result of ischemic infarction involving subcortical structures such as mollaret triangle, thalamus, and basal ganglia. However, it is novel for frontal cortical infarcts to present with acute‐onset contralateral limb tremor, especially as an isolated symptom. Our case suggests a “secondary insult” involving the frontal cortex can disinhibit the motor pathway that leads to tremor in preexisting midbrain and thalamic lesions. We present a 67‐year‐old male with acute onset, constant, rhythmic tremor in the setting of acute ischemic frontal cortical infarction. Methods: n/a, case report Results: A 67‐year‐old male with medical history of pineal gland cyst status‐post shunt placement and hypertension who presented for evaluation of acute onset right upper extremity rhythmic tremor that started 24 hours prior. He did not have any associated weakness, numbness, vision changes, nausea, or vomiting. He had never had this tremor before. Neurologic examination was significant for a 4.0 Hz rhythmic resting tremor that was present throughout exam and was non‐distractible. This tremor remained consistent even with kinetic movements and postures. Electroencephalogram (EEG) was performed STAT during this tremor and was not based in seizure. Non‐contrast head computerized tomography (CT) was negative for any acute hemorrhage or intracranial pathology. CT angiogram head and neck showed left internal carotid artery (ICA) long segment tapered occlusion from the proximal cervical ICA to the distal petrous segment, likely dissection of undetermined chronicity. Magnetic resonance imaging (MRI) Brain with and without contrast was significant for acute punctate foci involving the precentral cortex of the left frontal lobe consistent with acute ischemic infarction. Encephalomalacia was also present involving the bilateral posterior thalami and left midbrain chronic ischemic infarctions. This suggests the tremor was caused by disinhibition of the motor pathway from the ischemic insult to the frontal cortex, as he had pre‐existing asymptomatic ischemic insult to the typical structures known to cause this tremor. He was outside of the Tenecteplase window and was given a load of Aspirin followed by aspirin 81 mg daily. He was trialed on propranolol for treatment of symptomatic tremor however this was discontinued before discharge as it was ineffective and patient preferred to hold off on other treatments. He is now awaiting outpatient Neurology follow up. Conclusion: This case suggests that acute onset Holmes tremor can be the sole presenting sign in acute ischemic frontal cortical infarction. The pre‐existing asymptomatic infarctions in the midbrain and thalamus also support that a “second hit” located in the frontal cortex can disinhibit the motor pathway between the cortex and rubral tract. This is important as Holmes tremor is more commonly known to be from a mechanism of damage to the red nucleus or thalamic structures in a delayed manner, typically at least two weeks after stroke. This knowledge will help identify rare strokes in a timely manner.

Summary: Over the past 3 decades, tests of autonomic function have become increasingly standardized across most laboratories, particularly with commercially available equipment similar to other neurophysiologic tests. Most neurologically based laboratories perform four or five tests of autonomic function. Two of these, the sudomotor axon reflex response and the thermoregulatory sweat test (which some laboratories do not perform because it requires extensive equipment), examine sudomotor autonomic function. The remaining three, the cardiovascular response to a tilt table test, the cardiovascular response to the Valsalva maneuver, and the cardiac response to deep breathing examine cardiovascular autonomic function. Tests of sweating typically localize the lesion in the neuraxis, differentiating between central nervous system pathways, the spinal cord, or pre- or postganglionic roots or nerves. Tests of cardiovascular function delineate specific autonomic subsystem involvement, whether vagal parasympathetic as reflected in the deep breathing response and specific phases of the Valsalva maneuver or sympathetic adrenergic as reflected in the tilt table test and the other phases of the Valsalva. This review details the basic performance, analysis, and interpretation of these and a few other tests, with illustrative patient cases.

Aims: The neuropathophysiology of a debilitating chronic urologic pain condition, bladder pain syndrome (BPS), remains unknown. Our recent data suggests withdrawal of cardiovagal modulation in subjects with BPS, in contrast to sympathetic nervous system dysfunction in another chronic pelvic pain syndrome, myofascial pelvic pain (MPP). We evaluated whether comorbid disorders differentially associated with BPS vs MPP shed additional light on these autonomic differences.Methods: We compared the presence and relative time of onset of 27 other medical conditions in women with BPS, MPP, both syndromes, and healthy subjects. Analysis included an adjustment for multiple comparisons.Results: Among 107 female subjects (BPS alone = 32; BPS with MPP = 36; MPP alone = 9; healthy controls = 30), comorbidities differentially associated with BPS included irritable bowel syndrome (IBS), dyspepsia, and chronic nausea, whereas those associated with MPP included migraine headache and dyspepsia, consistent with the distinct autonomic neurophysiologic signatures of the two disorders. PTSD (earliest), anxiety, depression, migraine headache, fibromyalgia, chronic fatigue, and IBS usually preceded BPS or MPP. PTSD and the presence of both pelvic pain disorders in the same subject correlated with significantly increased comorbid burden.Conclusions: Our study suggests a distinct pattern of comorbid conditions in women with BPS. These findings further support our hypothesis of primary vagal defect in BPS as compared with primary sympathetic defect in MPP, suggesting a new model for chronic these pelvic pain syndromes. Chronologically, PTSD, migraine, dysmenorrhea, and IBS occurred early, supporting a role for PTSD or its trigger in the pathophysiology of chronic pelvic pain.

Aim: To describe a sensory map of pelvic dermatomes in women with Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS). We hypothesized that if IC/BPS involves changes in central processing, then women with IC/BPS will exhibit sensory abnormalities in neurologic pelvic dermatomes.Methods: Women with IC/BPS and healthy controls underwent neurologic examination that included evaluation of sharp pain sensitivity and vibration in dermatomes T12, L1, L2, S1‐5. Peripheral nervous system sensitivity to pressure, vibration, and pinprick were scored using numeric rating scales (NRS). Bilateral comparisons were made with Wilcoxon signed‐rank test and comparisons between groups were made by the Mann‐Whitney U‐test.Results: Total of 74 women with IC/BPS and 36 healthy counterparts were included. IC/BPS and control groups had similar age (43.0 ± 14.1 and 38.6 ± 15.3 years, P = 0.14) and BMI (28.9 ± 8.0 kg/m² and 26.9 ± 8.4 kg/m², P = 0.24), respectively. Women with IC/BPS reported hyperalgesia (elevated bilateral NRS pain intensity) in all pelvic dermatomes compared to healthy controls. S4‐S5 region had the highest pain intensity in all participants. All IC/BPS participants exhibited vibration sensation hypoesthesia, at least unilaterally, in all of the pelvic dermatomes except L1 compared to healthy controls.Conclusion: This detailed map of neurologic pelvic dermatomes in women with IC/BPS found hyperalgesia in all pelvic dermatomes, and some evidence of vibration sensation hypoesthesia, compared to healthy controls. These findings support the hypothesis that IC/BPS may involve changes in central signal processing biased towards nociception.

We determined whether abnormal autonomic nervous system innervation of the bladder underlies IC (interstitial cystitis)/BPS (bladder pain syndrome) differently than other chronic pelvic pain. In this institutional review board approved protocol 39 healthy controls and 134 subjects were enrolled, including 36 with IC/BPS, 14 with myofascial pelvic pain and 42 with IC/BPS plus myofascial pelvic pain. Three subjects were excluded from study. Autonomic nervous system evaluations included deep breathing, the Valsalva maneuver, and the tilt table and sudomotor tests. The latter evaluates autonomic neuropathy. A modified validated composite autonomic laboratory score was applied. Median age in the IC/BPS group was 47.5 years (range 21 to 78), greater than in healthy controls (34 years, range 20 to 75, p = 0.006), the myofascial pelvic pain group (33 years, range 22 to 56, p = 0.004) and the IC/BPS plus myofascial pelvic pain group (38 years, range 18 to 64, p = 0.03). Body mass index did not significantly differ but the myofascial pelvic pain and IC/BPS plus myofascial pelvic pain groups had a higher body mass index than healthy controls (p = 0.05 and 0.03, respectively). Cardiovascular and adrenergic indexes did not differ. The tilt table test showed more orthostatic intolerance in all chronic pelvic pain groups. Tilt table test diagnoses (orthostatic hypotension, postural tachycardia syndrome and reflex syncope) were rare. Baseline heart rate was higher in all chronic pelvic pain groups (p = 0.004). Compared to healthy controls all myofascial pelvic pain groups showed significantly more clear-cut autonomic neuropathy, defined as a sweat score of 3 or greater (vs IC/BPS plus myofascial pelvic pain p = 0.007 and vs myofascial pelvic pain p = 0.03). Some chronic pelvic pain types show autonomic neuropathy and some show vagal withdrawal. In all types orthostatic intolerance likely reflects central sensitization and perhaps catastrophizing. Some of these findings suggest novel therapeutic targets.