The funduscopic examination can be a technically difficult, and often omitted, portion of the neurologic examination, despite its great potential to influence patient care.
Medical practitioners are ...often first taught to examine the ocular fundus using a direct ophthalmoscope, however, this skill requires frequent practice. Nonmydriatic tabletop and portable fundus photography and even smartphone-based photography offer alternative and practical means for approaching examination of the ocular fundus. These alternative tools have been shown to be practical in a variety of settings including ambulatory clinics and emergency departments. Decreased retinal microvascular density detected with fundus photography has been linked to accelerated rates of cognitive decline. Research has also found optic disc pallor and retinopathy detected via fundus photography to be more prevalent in patients with recent stroke or transient ischemic attack.
Alternative methods of funduscopic examination based on fundus photography have the potential to improve the ease of use, portability, and availability of funduscopy. Recognition of changes in retinal microvasculature has the potential to noninvasively identify patients at the highest risk for cognitive impairment and cerebrovascular disease. However, further research is needed to determine the specific utility of measurements of retinal microvascular changes in clinical care. Innovative funduscopy techniques offer neurologists new approaches to this essential facet of the neurological examination.
The clinical characteristics of patients with polymerase gamma (POLG) mutation-associated optic neuropathy remain incompletely characterized.
We describe the clinical characteristics of 3 patients ...with POLG-associated optic neuropathy. We performed a literature review of optic neuropathy cases associated with POLG mutations and compared them with our cohort.
Many published cases of POLG-associated optic neuropathy in our literature review lacked details regarding severity of vision loss, visual field defects, and optical coherence tomography analysis. The clinical presentation of POLG mutations remains widely variable in age (from pediatric cases to adults) and associated systemic findings. All patients in our literature review presented with systemic symptoms, most commonly muscle weakness, ptosis, and ophthalmoplegia, whereas many young patients had severe systemic symptoms. In our case series, all 3 cases had isolated optic neuropathy affecting the papillomacular bundle, with signs such as reduced visual acuity and color vision, central visual field defects, temporal retinal nerve fiber layer loss with temporal optic disc pallor, and retinal ganglion cell complex loss. In addition, 2 of the 3 cases had added mitochondrial stressors in addition to the POLG mutation.
Clinicians should be aware that POLG mutations can present as isolated optic neuropathy primarily affecting the papillomacular bundle. With mitochondrial failure being the likely underlying pathogenic mechanism in POLG-associated optic neuropathy, helping affected patients eliminate mitochondrial stressors may be important in reducing the risk for progressive vision loss in this otherwise currently untreatable disorder.
Inspiratory neurons of the preBötzinger complex (preBötC) form local excitatory networks and display 10–30 mV transient depolarizations, dubbed inspiratory drive potentials, with superimposed ...spiking. AMPA receptors are critical for rhythmogenesis under normal conditions in vitro but whether other postsynaptic mechanisms contribute to drive potential generation remains unknown. We examined synaptic and intrinsic membrane properties that generate inspiratory drive potentials in preBötC neurons using neonatal mouse medullary slice preparations that generate respiratory rhythm. We found that NMDA receptors, group I metabotropic glutamate receptors (mGluRs), but not group II mGluRs, contributed to inspiratory drive potentials. Subtype 1 of the group I mGluR family (mGluR1) probably regulates a K+ channel, whereas mGluR5 operates via an inositol 1,4,5‐trisphosphate (IP3) receptor‐dependent mechanism to augment drive potential generation. We tested for and verified the presence of a Ca2+‐activated non‐specific cation current (ICAN) in preBötC neurons. We also found that high concentrations of intracellular BAPTA, a high‐affinity Ca2+ chelator, and the ICAN antagonist flufenamic acid (FFA) decreased the magnitude of drive potentials. We conclude that ICAN underlies robust inspiratory drive potentials in preBötC neurons, and is only fully evoked by ionotropic and metabotropic glutamatergic synaptic inputs, i.e. by network activity.
BACKGROUND:Central venous obstruction (stenosis or occlusion) is common in patients with renal failure on hemodialysis and may be associated with intracranial hypertension (IH). Causes include vein ...injury from an endoluminal device, lumen obstruction from a device or thrombus, external vein compression, and high venous flow leading to vein intimal hyperplasia. A combination of high venous flow and central venous obstruction can lead to intracranial venous hypertension, impaired cerebrospinal fluid (CSF) resorption, and subsequent IH.
EVIDENCE ACQUISITION:We conducted a search of the English literature using the Ovid MEDLINE Database and PubMed, with a focus on reports involving IH and central venous obstruction in the setting of hemodialysis. We reviewed CSF flow dynamics, the risk factors and causes of central venous obstruction, and the evaluation, management, and outcomes of central venous obstruction-induced IH.
RESULTS:Twenty-four cases of IH related to central venous obstruction in hemodialysis patients were identified. Twenty patients had headaches (83.3%) and 9 had visual symptoms (37.5%). The brachiocephalic vein was the most common site of stenosis or occlusion (20/24, 83.3%). Twenty-one patients (87.5%) had resolution of IH with treatment. Two patients died from complications of IH (8.3%).
CONCLUSIONS:Central venous obstruction–induced IH is likely underrecognized by clinicians and mimics idiopathic IH. Hemodialysis patients with IH should be screened with computed tomography venography of the chest. Optimal treatment is with vascular intervention or a CSF diversion procedure and can help prevent vision loss from papilledema or nervous system damage. Medical management may be appropriate in mild cases or as a bridge to definitive interventional treatment. Increased awareness among clinicians has potential to facilitate the timely diagnosis of this treatable condition with potential for good neurologic and visual outcomes.
Referral Patterns in Neuro-Ophthalmology Stunkel, Leanne; Mackay, Devin D; Bruce, Beau B ...
Journal of neuro-ophthalmology,
2020-December, 2020-12-00, 20201201, Letnik:
40, Številka:
4
Journal Article
Recenzirano
Odprti dostop
BACKGROUND:Neuro-ophthalmologists specialize in complex, urgent, vision- and life-threatening problems, diagnostic dilemmas, and management of complex work-ups. Access is currently limited by the ...relatively small number of neuro-ophthalmologists, and consequently, patients may be affected by incorrect or delayed diagnosis. The objective of this study is to analyze referral patterns to neuro-ophthalmologists, characterize rates of misdiagnoses and delayed diagnoses in patients ultimately referred, and delineate outcomes after neuro-ophthalmologic evaluation.
METHODS:Retrospective chart review of 300 new patients seen over 45 randomly chosen days between June 2011 and June 2015 in one tertiary care neuro-ophthalmology clinic. Demographics, distance traveled, time between onset and neuro-ophthalmology consultation (NOC), time between appointment request and NOC, number and types of providers seen before referral, unnecessary tests before referral, referral diagnoses, final diagnoses, and impact of the NOC on outcome were collected.
RESULTS:Patients traveled a median of 36.5 miles (interquartile range IQR20–85). Median time from symptom onset was 210 days (IQR70–1,100). Median time from referral to NOC was 34 days (IQR7–86), with peaks at one week (urgent requests) and 13 weeks (routine requests). Median number of previous providers seen was 2 (IQR2–4; range:0–10), and 102 patients (34%) had seen multiple providers within the same specialty before referral. Patients were most commonly referred for NOC by ophthalmologists (41% of referrals). Eighty-one percent (242/300) of referrals to neuro-ophthalmology were appropriate referrals. Of the 300 patients referred, 247 (82%) were complex or very complex; 119 (40%) were misdiagnosed; 147 (49%) were at least partially misdiagnosed; and 22 (7%) had unknown diagnoses. Women were more likely to be at least partially misdiagnosed—108 of 188 (57%) vs 39 of 112 (35%) of men (P < 0.001). Mismanagement or delay in care occurred in 85 (28%), unnecessary tests in 56 (19%), unnecessary consultations in 64 (22%), and imaging misinterpretation in 16 (5%). Neuro-ophthalmologists played a major role in directing treatment, such as preserving vision, preventing life-threatening complications, or avoiding harmful treatment in 62 (21%) patients.
CONCLUSIONS:Most referrals to neuro-ophthalmologists are appropriate, but many are delayed. Misdiagnosis before referral is common. Neuro-ophthalmologists often prevent vision- and life-threatening complications.
Breathing movements in mammals depend on respiratory neurons in the preBötzinger Complex (preBötC), which comprise a rhythmic network and generate robust bursts that form the basis for inspiration. ...Persistent Na+ current (INaP) is widespread in the preBötC and is hypothesized to play a critical role in rhythm generation because of its subthreshold activation and slow inactivation properties that putatively promote long‐lasting burst depolarizations. In neonatal mouse slice preparations that retain the preBötC and generate a respiratory‐related rhythm, we tested the role of INaP with multiple Na+ channel antagonists: tetrodotoxin (TTX; 20 nm), riluzole (RIL; 10 μm), and the intracellular Na+ channel antagonist QX‐314 (2 mm). Here we show that INaP promotes intraburst spiking in preBötC neurons but surprisingly does not contribute to the depolarization that underlies inspiratory bursts, i.e. the inspiratory drive potential. Local microinjection in the preBötC of 10 μm RIL or 20 nm TTX does not perturb respiratory frequency, even in the presence of bath‐applied 100 μm flufenamic acid (FFA), which attenuates a Ca2+‐activated non‐specific cation current (ICAN) that may also have burst‐generating functionality. These data contradict the hypothesis that INaP in preBötC neurons is obligatory for rhythmogenesis. However, in the presence of FFA, local microinjection of 10 μm RIL in the raphe obscurus causes rhythm cessation, which suggests that INaP regulates the excitability of neurons outside the preBötC, including serotonergic raphe neurons that project to, and help maintain, rhythmic preBötC function.
The eye has been considered a 'window to the brain,' and several neurological diseases including neurodegenerative conditions like Alzheimer's disease (AD) also show changes in the retina.
To ...investigate retinal nerve fiber layer (RNFL) thickness and its association with brain volume via magnetic resonance imaging (MRI) in older adults with subjective or objective cognitive decline.
75 participants underwent ophthalmological and neurological evaluation including optical coherence tomography and MRI (28 cognitively normal subjects, 26 with subjective cognitive decline, 17 patients diagnosed with mild cognitive impairment, and 4 with AD). Differences in demographics, thickness of RNFL, and brain volume were assessed using ANCOVA, while partial Pearson correlations, covaried for age and sex, were used to compare thickness of the peripapillary RNFL with brain volumes, with p < 0.05 considered statistically significant.
Mean RNFL thickness was significantly correlated with brain volumes, including global volume (right eye r = 0.235 p = 0.046, left eye r = 0.244, p = 0.037), temporal lobe (right eye r = 0.242 p = 0.039, left eye r = 0.290, p = 0.013), hippocampal (right eye r = 0.320 p = 0.005, left eye r = 0.306, p = 0.008), amygdala (left eye r = 0.332, p = 0.004), and occipital lobe (right eye r = 0.264 p = 0.024) volumes.
RNFL thickness in both eyes was positively associated with brain volumes in subjects with subjective and objective cognitive decline. The RNFL, however, did not correlate with the disease, but the small sample number makes it important to conduct larger studies. RNFL thickness may be a useful non-invasive and inexpensive tool for detection of brain neurodegeneration and may assist with diagnosis and monitoring of progression and treatment in AD.
The breathing motor pattern in mammals originates in brainstem networks. Whether pacemaker neurons play an obligatory role remains a key unanswered question. We performed whole-cell recordings in the ...preBotzinger Complex in slice preparations from neonatal rodents and tested for pacemaker activity. We observed persistent Na+ current (I(NaP))-mediated bursting in approximately 5% of inspiratory neurons in postnatal day 0 (P0)-P5 and in P8-P10 slices. I(NaP)-mediated bursting was voltage dependent and blocked by 20 mum riluzole (RIL). We found Ca2+ current (I(Ca))-dependent bursting in 7.5% of inspiratory neurons in P8-P10 slices, but in P0-P5 slices these cells were exceedingly rare (0.6%). This bursting was voltage independent and blocked by 100 microm Cd2+ or flufenamic acid (FFA) (10-200 microm), which suggests that a Ca2+-activated inward cationic current (I(CAN)) underlies burst generation. These data substantiate our observation that P0-P5 slices exposed to RIL contain few (if any) pacemaker neurons, yet maintain respiratory rhythm. We also show that 20 nm TTX or coapplication of 20 microm RIL + FFA (100-200 microm) stops the respiratory rhythm, but that adding 2 mum substance P restarts it. We conclude that I(NaP) and I(CAN) enhance neuronal excitability and promote rhythmogenesis, even if their magnitude is insufficient to support bursting-pacemaker activity in individual neurons. When I(NaP) and I(CAN) are removed pharmacologically, the rhythm can be maintained by boosting neural excitability, which is inconsistent with a pacemaker-essential mechanism of respiratory rhythmogenesis by the preBotzinger complex.
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