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1.
Ann Neurol ; 94(2): 295-308, 2023 08.
Article in English | MEDLINE | ID: mdl-37038843

ABSTRACT

OBJECTIVE: Acute dizziness/vertigo is usually due to benign inner-ear causes but is occasionally due to dangerous neurologic ones, particularly stroke. Because symptoms and signs overlap, misdiagnosis is frequent and overuse of neuroimaging is common. We assessed the accuracy of bedside findings to differentiate peripheral vestibular from central neurologic causes. METHODS: We performed a systematic search (MEDLINE and Embase) to identify studies reporting on diagnostic accuracy of physical examination in adults with acute, prolonged dizziness/vertigo ("acute vestibular syndrome" [AVS]). Diagnostic test properties were calculated for findings. Results were stratified by examiner type and stroke location. RESULTS: We identified 6,089 citations and included 14 articles representing 10 study cohorts (n = 800). The Head Impulse, Nystagmus, Test of Skew (HINTS) eye movement battery had high sensitivity 95.3% (95% confidence interval [CI] = 92.5-98.1) and specificity 92.6% (95% CI = 88.6-96.5). Sensitivity was similar by examiner type (subspecialists 94.3% [95% CI = 88.2-100.0] vs non-subspecialists 95.0% [95% CI = 91.2-98.9], p = 0.55), but specificity was higher among subspecialists (97.6% [95% CI = 94.9-100.0] vs 89.1% [95% CI = 83.0-95.2], p = 0.007). HINTS sensitivity was lower in anterior cerebellar artery (AICA) than posterior inferior cerebellar artery (PICA) strokes (84.0% [95% CI = 65.3-93.6] vs 97.7% [95% CI = 93.3-99.2], p = 0.014) but was "rescued" by the addition of bedside hearing tests (HINTS+). Severe (grade 3) gait/truncal instability had high specificity 99.2% (95% CI = 97.8-100.0) but low sensitivity 35.8% (95% CI = 5.2-66.5). Early magnetic resonance imaging (MRI)-diffusion-weighted imaging (DWI; within 24-48 hours) was falsely negative in 15% of strokes (sensitivity 85.1% [95% CI = 79.2-91.0]). INTERPRETATION: In AVS, HINTS examination by appropriately trained clinicians can differentiate peripheral from central causes and has higher diagnostic accuracy for stroke than MRI-DWI in the first 24-48 hours. These techniques should be disseminated to all clinicians evaluating dizziness/vertigo. ANN NEUROL 2023;94:295-308.


Subject(s)
Nystagmus, Pathologic , Stroke , Adult , Humans , Dizziness/etiology , Dizziness/complications , Vertigo/diagnosis , Vertigo/etiology , Eye Movements , Nystagmus, Pathologic/complications , Nystagmus, Pathologic/diagnosis , Stroke/complications , Stroke/diagnosis , Acute Disease , Diagnostic Tests, Routine/adverse effects
2.
Parasitol Res ; 123(4): 180, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38592544

ABSTRACT

Because of recent reports of praziquantel resistance in schistosome infections, there have been suggestions to employ ivermectin as a possible alternative, especially as its chemical composition is different from that of praziquantel, so cross-resistance is not expected. In order to ascertain possible damage and elimination of worms, we used ivermectin by oral gavage in infected mice, at a high dose (30.1 mg/kg, bordering toxicity). We also tested the efficacy of the drug at various times postinfection (PI), to check on possible effect on young and mature stages of the parasites. Thus, we treated mice on days 21 and 22 or on days 41 and 42 and even on days 21, 22, 41, and 42 PI. None of the treatment regimens resulted in cure rates or signs of lessened pathology in the mice. We also compared the effect of ivermectin to that of artemisone, an artemisinin derivative which had served us in the past as an effective anti-schistosome drug, and there was a stark difference in the artemisone's efficacy compared to that of ivermectin; while ivermectin was not effective, artemisone eliminated most of the worms, prevented egg production and granulomatous inflammatory response. We assume that the reported lack of activity of ivermectin, in comparison with praziquantel and artemisinins, originates from the difference in their mode of action. In wake of our results, we suggest that ivermectin is not a suitable drug for treatment of schistosomiasis.


Subject(s)
Artemisinins , Schistosomatidae , Schistosomiasis , Animals , Mice , Praziquantel/therapeutic use , Ivermectin/therapeutic use , Schistosomiasis/drug therapy
3.
Curr Opin Neurol ; 36(1): 36-42, 2023 02 01.
Article in English | MEDLINE | ID: mdl-36380583

ABSTRACT

PURPOSE OF REVIEW: Recent updates with clinical implications in the field of neuro-otology are reviewed. RECENT FINDINGS: Important updates relating to several neuro-otologic disorders have been reported in recent years. For benign positional paroxysmal vertigo (BPPV), we provide updates on the characteristics and features of the short arm variant of posterior canal BPPV. For the acute vestibular syndrome, we report important updates on the use of video-oculography in clinical diagnosis. For autoimmune causes of neuro-otologic symptoms, we describe the clinical and paraclinical features of kelch-like protein 11 encephalitis, a newly-identified antibody associated disorder. For cerebellar ataxia, neuropathy, vestibular areflexia syndrome, we report recent genetic insights into this condition. SUMMARY: This review summarizes important recent updates relating to four hot topics in neuro-otology.


Subject(s)
Neurotology , Humans , Benign Paroxysmal Positional Vertigo/diagnosis
4.
Catheter Cardiovasc Interv ; 102(6): 997-1003, 2023 11.
Article in English | MEDLINE | ID: mdl-37890004

ABSTRACT

BACKGROUND: The safety and efficacy of intravascular lithotripsy (IVL) for the treatment of calcified distal left main (LM) disease remains unclear, especially compared to rotational atherectomy (RA). METHODS: We retrospectively analyzed the baseline clinical, angiographic, intravascular ultrasound (IVUS) characteristics and procedural outcomes of 107 patients who underwent distal LM percutaneous coronary intervention (PCI) with IVL (with or without adjunct atherectomy) versus RA alone for plaque modification before stenting at a single center between 2020 and 2022. RESULTS: A total of 50 patients underwent calcium modification with IVL with or without adjunct atherectomy and 57 with RA only. The mean age was 73 years and with a high prevalence of diabetes (58.9%), chronic kidney disease (42.1%), prior revascularization (coronary artery bypass graft surgery [36.4%] or prior PCI [32.7%]). Acute coronary syndrome was the primary indication for PCI in over 50% of the patients in both groups. Medina 1-1-1 LM bifurcation disease was identified in 64% and 60% of the IVL and RA groups (p = 0.64) respectively. Final minimum stent area in distal LM (>8.2 mm2 ), ostial LAD (>6.3 mm2 ) and ostial LCX (>5.0 mm2 ) were achieved in 96%, 85% and 89% of cases treated with IVL respectively and 93%, 93% and 100% of cases treated with RA respectively (LM p = 1.00; LAD p = 0.62; LCX; p = 1.00 for difference between the two groups). Procedural success (technical success without in-hospital major adverse events) was achieved in 98% of the IVL group and 86% of the RA-only group (p = 0.04). There were eight procedural complications (flow-limiting dissection, perforation, or slow/no-reflow) in the RA group compared to four in the IVL group (NS), and one patient in the RA required salvaged mechanical support compared to none in the IVL group. CONCLUSION: Plaque modification with coronary IVL appears to be efficacious and safe for the treatment of severely calcified distal LM lesions compared to RA only. Larger randomized studies are needed to confirm these findings.


Subject(s)
Atherectomy, Coronary , Coronary Artery Disease , Lithotripsy , Percutaneous Coronary Intervention , Plaque, Atherosclerotic , Vascular Calcification , Humans , Aged , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/therapy , Coronary Artery Disease/etiology , Atherectomy, Coronary/adverse effects , Percutaneous Coronary Intervention/adverse effects , Retrospective Studies , Coronary Angiography , Treatment Outcome , Vascular Calcification/diagnostic imaging , Vascular Calcification/therapy , Vascular Calcification/etiology , Lithotripsy/adverse effects
5.
J Neuroophthalmol ; 43(2): 273-276, 2023 06 01.
Article in English | MEDLINE | ID: mdl-36728609

ABSTRACT

ABSTRACT: A 68-year-old woman with positional dizziness and progressive imbalance presented for vestibular evaluation. Examination was notable for spontaneous downbeat nystagmus (DBN), horizontal and vertical gaze-evoked nystagmus (GEN) with centripetal and rebound nystagmus, and positional apogeotropic nystagmus. There was also mild-moderate slowing of saccades horizontally and vertically and poor fast phases with an optokinetic stimulus. Further consultation by a movement disorder specialist uncovered asymmetric decrementing bradykinesia and rigidity, masked facies, and a wide-based stance without camptocormia. Screening serum laboratory results for metabolic, rheumatologic, infectious, heavy metal, endocrine, or vitamin abnormalities was normal. Surveillance imaging for neoplasms was unremarkable, and cerebrospinal fluid (CSF) analysis was negative for 14-3-3 and real-time quaking-induced conversion (RT-QuIC). However, her anti-glutamic acid decarboxylase-65 (GAD65) immunoglobulin G (IgG) level was markedly elevated in serum to 426,202 IU/mL (reference range 0-5 IU/mL) and in CSF to 18.1 nmol/L (reference range <0.03 nmol/L). No other autoantibodies were identified on the expanded paraneoplastic panel. The patient was referred to neuroimmunology, where torso rigidity, spasticity, and significant paravertebral muscle spasms were noted. Overall, the clinical presentation, examination findings, and extensive workup were consistent with a diagnosis of anti-GAD65-associated stiff person syndrome-plus (musculoskeletal plus cerebellar and/or brainstem involvement). She was subsequently treated with intravenous immunoglobulin (IVIg) and has been stable since commencing this therapy. In patients with centripetal nystagmus, especially in association with other cerebellar findings, an autoimmune cerebellar workup should be considered.


Subject(s)
Cerebellar Ataxia , Nystagmus, Pathologic , Parkinsonian Disorders , Stiff-Person Syndrome , Female , Humans , Aged , Saccades , Stiff-Person Syndrome/complications , Stiff-Person Syndrome/diagnosis , Stiff-Person Syndrome/drug therapy , Glutamate Decarboxylase , Nystagmus, Pathologic/diagnosis , Nystagmus, Pathologic/etiology , Nystagmus, Pathologic/drug therapy , Autoantibodies , Parkinsonian Disorders/complications , Parkinsonian Disorders/diagnosis
6.
Curr Opin Neurol ; 35(1): 75-83, 2022 02 01.
Article in English | MEDLINE | ID: mdl-34889806

ABSTRACT

PURPOSE OF REVIEW: We present here neuro-otological tests using portable video-oculography (VOG) and strategies assisting physicians in the process of decision making beyond the classical 'HINTS' testing battery at the bedside. RECENT FINDINGS: Patients with acute vestibular syndrome (AVS) experience dizziness, gait unsteadiness and nausea/vomiting. A variety of causes can lead to this condition, including strokes. These patients cannot be adequately identified with the conventional approach by stratifying based on risk factors and symptom type. In addition to bedside methods such as HINTS and HINTS plus, quantitative methods for recording eye movements using VOG can augment the ability to diagnose and localize the lesion. In particular, the ability to identify and quantify the head impulse test (VOR gain, saccade metrics), nystagmus characteristics (waveform, beating direction and intensity), skew deviation, audiometry and lateropulsion expands our diagnostic capabilities. In addition to telemedicine, algorithms and artificial intelligence can be used to support emergency physicians and nonexperts in the future. SUMMARY: VOG, telemedicine and artificial intelligence may assist physicians in the diagnostic process of AVS patients.


Subject(s)
Artificial Intelligence , Vertigo , Head Impulse Test , Humans , Nausea , Vomiting
7.
EMBO Rep ; 21(1): e47882, 2020 01 07.
Article in English | MEDLINE | ID: mdl-31825165

ABSTRACT

During the chronic stage of Schistosoma infection, the female lays fertile eggs, triggering a strong anti-parasitic type 2 helper T-cell (Th2) immune response. It is unclear how this Th2 response gradually declines even though the worms live for years and continue to produce eggs. Here, we show that Schistosoma mansoni downregulates Th2 differentiation in an antigen-presenting cell-independent manner, by modulating the Th2-specific transcriptional program. Adult schistosomes secrete miRNA-harboring extracellular vesicles that are internalized by Th cells in vitro. Schistosomal miRNAs are found also in T helper cells isolated from Peyer's patches and mesenteric lymph nodes of infected mice. In T helper cells, the schistosomal miR-10 targets MAP3K7 and consequently downmodulates NF-κB activity, a critical transcription factor for Th2 differentiation and function. Our results explain, at least partially, how schistosomes tune down the Th2 response, and provide further insight into the reciprocal geographic distribution between high prevalence of parasitic infections and immune disorders such as allergy. Furthermore, this worm-host crosstalk mechanism can be harnessed to develop diagnostic and therapeutic approaches for human schistosomiasis and Th2-associated diseases.


Subject(s)
Extracellular Vesicles , MicroRNAs , Animals , Cell Differentiation , Female , Mice , MicroRNAs/genetics , Schistosoma mansoni/genetics , Th2 Cells
8.
BMC Infect Dis ; 22(1): 16, 2022 Jan 04.
Article in English | MEDLINE | ID: mdl-34983409

ABSTRACT

BACKGROUND: Enterovirus has been described as a cause of aseptic meningitis in humorally immunosuppressed patients. CASE PRESENTATION: A 67-year-old female with a history of mantle cell lymphoma on rituximab therapy presented with subacute hepatitis, myalgias, and sensorineural hearing loss several months after an initial febrile illness. She was diagnosed with enterovirus infection by CSF PCR as a unifying etiology of her presentation, representing an unusual presentation of disease. DISCUSSION AND CONCLUSIONS: This patient's unique presentation and clinical course presents important implications in the care of similarly immunosuppressed patients with cryptic complaints.


Subject(s)
Enterovirus Infections , Enterovirus , Hearing Loss, Sensorineural , Meningitis, Aseptic , Meningitis , Aged , Enterovirus Infections/complications , Enterovirus Infections/diagnosis , Female , Humans , Meningitis, Aseptic/diagnosis
9.
Curr Neurol Neurosci Rep ; 22(3): 219-228, 2022 03.
Article in English | MEDLINE | ID: mdl-35235169

ABSTRACT

PURPOSE OF REVIEW: Mild traumatic brain injury, or concussion, is a major cause of disability. Vestibular and visual dysfunction following concussion is common and can negatively affect patients' well-being and prolong recovery. Etiologies of visual and vestibular symptoms are numerous, including ocular, neuro-ophthalmic, otologic, and neuro-vestibular conditions. Some etiologies are benign and may be treatable, while others are potentially vision or life-threatening, making a focused history and examination essential. This review offers an approach to the evaluation and treatment of the most common neuro-visual and vestibular impairments that may result from concussion. RECENT FINDINGS: Treatment of concussion including exercise, computerized programs, transcranial magnetic stimulation, gene therapy, stem cell therapy, and nanoparticles has shown promise. Many novel therapies are in the pipework for visual and vestibular recovery after concussion; however, the treatment mainstay remains therapy and evaluation for co-existing diseases.


Subject(s)
Brain Concussion , Vestibular Diseases , Brain Concussion/complications , Brain Concussion/diagnosis , Brain Concussion/therapy , Humans , Vestibular Diseases/diagnosis , Vestibular Diseases/etiology , Vestibular Diseases/therapy , Vision Disorders/complications , Vision Disorders/etiology
10.
Cerebellum ; 20(5): 734-743, 2021 Oct.
Article in English | MEDLINE | ID: mdl-31883062

ABSTRACT

The pathophysiology of acute, vertical spontaneous eye movements following pontine hemorrhage is not well understood. Here, we present and discuss the video-oculography findings of a patient with acute pontine hemorrhage who developed vertical pendular oscillation and ocular bobbing while comatose. The amplitudes, peak velocities, frequency distribution, and phase planes (velocity versus position) of the eye movements were analyzed. The vertical pendular oscillation was rhythmic with a peak frequency of 1.7 Hz, but amplitudes (mean 1.9°, range 0.2-8.2°) and peak velocities (mean 20.6°/s; range 5.9-60.6°/sec) fluctuated. Overall, their peak velocities were asymmetric, faster with downward than upward. Higher peak velocities were seen with larger amplitudes (downward phase r = 0.95, p < 0.001; upward phase r = 0.91, p < 0.001) and with movements beginning at eye positions lower in the orbit (downward phase r = - 0.64, p < 0.001; upward phase r = - 0.86, p < 0.001). Interspersed were typical ocular bobbing waveforms with a fast (peak velocity 128.8°/s), large-amplitude (17.5°) downward movement, sometimes followed by a flat interphase interval (0.5 s) when the eye was nearly stationary, and then a slow return to mid-position with a decaying velocity waveform. To account for the presence and co-existence of pendular oscillations and bobbing, we present and discuss three hypothetical models, not necessarily mutually exclusive: (1) oscillations originating in the inferior olives due to disruption of the central tegmental tract(s); (2) unstable neural integrator function due to pontine cell group damage involving neurons involved in gaze-holding; (3) low-frequency saccadic intrusions following omnipause neuron damage.


Subject(s)
Eye Movements , Ocular Motility Disorders , Cerebral Hemorrhage/complications , Humans , Ocular Motility Disorders/complications
11.
Cerebellum ; 20(1): 4-8, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32794025

ABSTRACT

The virtual practice has made major advances in the way that we care for patients in the modern era. The culture of virtual practice, consulting, and telemedicine, which had started several years ago, took an accelerated leap as humankind was challenged by the novel coronavirus pandemic (COVID19). The social distancing measures and lockdowns imposed in many countries left medical care providers with limited options in evaluating ambulatory patients, pushing the rapid transition to assessments via virtual platforms. In this novel arena of medical practice, which may form new norms beyond the current pandemic crisis, we found it critical to define guidelines on the recommended practice in neurotology, including remote methods in examining the vestibular and eye movement function. The proposed remote examination methods aim to reliably diagnose acute and subacute diseases of the inner-ear, brainstem, and the cerebellum. A key aim was to triage patients into those requiring urgent emergency room assessment versus non-urgent but expedited outpatient management. Physicians who had expertise in managing patients with vestibular disorders were invited to participate in the taskforce. The focus was on two topics: (1) an adequate eye movement and vestibular examination strategy using virtual platforms and (2) a decision pathway providing guidance about which patient should seek urgent medical care and which patient should have non-urgent but expedited outpatient management.


Subject(s)
COVID-19 , Neurologic Examination/methods , Telemedicine/methods , Triage/methods , Vestibular Diseases/diagnosis , Consensus , Humans , SARS-CoV-2
12.
Neurol Sci ; 42(12): 5343-5352, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34698943

ABSTRACT

BACKGROUND: Identifying dangerous causes of dizziness is a challenging task for neurologists, as it requires interpretation of subtle bedside exam findings, which become even more subtle with time. Nystagmus can be instrumental in differentiating peripheral from central vestibular disorders. Conventional teaching is that peripheral vestibular nystagmus is accentuated by removal of visual fixation. We sought to systematically test the hypothesis that, in some cases, vertical nystagmus due to central vestibular disorders may also be easier to identify when fixation is removed. METHODS: To identify patients with vertical nystagmus, we retrospectively reviewed clinical, MRI, and VNG data of consecutive patients undergoing VNG in our vestibular clinic over a 9-month period. We analyzed clinical features, bedside neuro-otological examination, MRI results, and VNG findings in fixation as well as those with fixation removed. RESULTS: Two hundred and fourteen charts were reviewed. Twenty-six patients had vertical nystagmus with fixation removed on VNG. Only three (11.5%) of these patients had vertical nystagmus apparent with fixation (and only two had nystagmus observed clearly at the bedside with the unaided eye). Thirteen (50%) of the patients had posterior fossa lesions on MRI and eight of the rest (30.8%) were diagnosed with central vestibular disorders. Of the 13 patients with MRI-confirmed lesions, 3 patients (23.1%) had no neurological signs or conventional bedside oculomotor signs; in these cases, vertical nystagmus without fixation was the only sign of a central lesion. CONCLUSIONS: Our findings go against conventional teaching and show that removing fixation can uncover subtle vertical nystagmus due to central vestibular disease, particularly from focal or chronic lesions.


Subject(s)
Nystagmus, Pathologic , Vestibular Diseases , Dizziness/diagnosis , Dizziness/etiology , Humans , Nystagmus, Pathologic/diagnosis , Retrospective Studies , Vertigo , Vestibular Diseases/complications , Vestibular Diseases/diagnosis
13.
J Neuroophthalmol ; 41(4): e672-e678, 2021 Dec 01.
Article in English | MEDLINE | ID: mdl-32701756

ABSTRACT

BACKGROUND: An ocular tilt reaction (OTR) is a triad of a skew deviation, head tilt, and ocular counter-roll that can be partial or complete. An OTR can occur anywhere along the utriculo-ocular motor pathways from the labyrinth to the interstitial nucleus of Cajal but is almost always central in origin. In acute vestibular neuritis (AVN), case reports have described patients with an OTR due to AVN, although it is unclear whether this examination finding is common or rare. METHODS: The vestibular and ocular motor features of 7 patients presenting with AVN are described. RESULTS: Each of the 7 patients presented with typical features of AVN, including contralesional unidirectional spontaneous nystagmus and an ipsilesional abnormal head impulse test, although each patient also had a complete OTR. None of the patients had vertical diplopia or a skew deviation that was measurable with alternate cover testing (i.e., abnormal "test of skew" according to the Head Impulse, Nystagmus, Test of Skew examination); however, all had a subtle 1 prism diopter hyperphoria that was only measurable with a Maddox rod test. CONCLUSION: Seven cases of typical AVN with an OTR are presented, and in the authors' experience, the presence of a subtle OTR is a common feature of AVN in these patients.


Subject(s)
Nystagmus, Pathologic , Ocular Motility Disorders , Strabismus , Vestibular Neuronitis , Diplopia/etiology , Humans , Nystagmus, Pathologic/diagnosis , Strabismus/diagnosis , Vestibular Neuronitis/complications , Vestibular Neuronitis/diagnosis
14.
J Neuroophthalmol ; 41(4): e665-e671, 2021 12 01.
Article in English | MEDLINE | ID: mdl-33105411

ABSTRACT

BACKGROUND: Antiglutamic acid decarboxylase (GAD)-associated neurologic disorders are rare, with varied presentations, including stiff-person syndrome (SPS) and cerebellar ataxia (CA). Vestibular and ocular motor (VOM) dysfunction can be the main presentation in a subset of patients. METHODS: Retrospective review of the Johns Hopkins Hospital medical records from 1997 to 2018 identified a total of 22 patients with a diagnosis of anti-GAD-associated SPS or CA who had detailed VOM assessments. Eight had prominent VOM dysfunction at the initial symptom onset and were referred to neurology from ophthalmology or otolaryngology ("early dominant"). Fourteen patients had VOM dysfunction that was not their dominant presentation and were referred later in their disease course from neurology to neuro-ophthalmology ("nondominant"). We reviewed clinical history, immunological profiles, and VOM findings, including available video-oculography. RESULTS: In the 8 patients with early dominant VOM dysfunction, the average age of symptom onset was 53 years, and 5 were men. The most common symptom was dizziness, followed by diplopia. Seven had features of CA, and 4 had additional features of SPS. None had a structural lesion on brain MRI accounting for their symptoms. The most common VOM abnormalities were downbeating and gaze-evoked nystagmus and saccadic pursuit. All received immune therapy and most received symptomatic therapy. Most experienced improvement in clinical outcome measures (modified Rankin scale and/or timed 25-foot walk test) or VOM function. By contrast, in the 14 patients in whom VOM dysfunction was nondominant, most had an SPS phenotype and were women. VOM abnormalities, when present, were more subtle, although mostly still consistent with cerebellar and/or brainstem dysfunction. CONCLUSIONS: Individuals with anti-GAD-associated neurologic disorders may present with prominent VOM abnormalities at the initial symptom onset that localize to the cerebellum and/or brainstem. In our cohort, immune and symptomatic therapies improved clinical outcomes and symptomatology.


Subject(s)
Carboxy-Lyases , Cerebellar Ataxia , Nervous System Diseases , Stiff-Person Syndrome , Carboxy-Lyases/therapeutic use , Cerebellar Ataxia/complications , Eye Movements , Female , Glutamate Decarboxylase , Humans , Stiff-Person Syndrome/complications , Stiff-Person Syndrome/diagnosis , Stiff-Person Syndrome/therapy
15.
J Neuroophthalmol ; 40(3): e49-e61, 2020 09.
Article in English | MEDLINE | ID: mdl-32804459

ABSTRACT

BACKGROUND: The visual, ocular motor and vestibular systems have intimate neural and close anatomical relationship that dictates their assessment in a patient with dizziness and vertigo. RESULTS: Recognition of the pearls and pitfalls of a targeted clinical examination HINTS/HINTS "Plus" allows the clinician to probe at the bedside the most crucial hypothesis in a patient with acute isolated vestibular syndrome, "Is this a stroke?" CONCLUSION: By applying a methodical approach to examination of patients with dizziness and vertigo, localization of the offending lesion, management, and even elucidation of the underlying diagnosis is feasible.


Subject(s)
Dizziness/diagnosis , Eye Movements/physiology , Vertigo/complications , Visual Acuity , Dizziness/etiology , Humans , Vertigo/diagnosis
16.
Semin Neurol ; 39(6): 761-774, 2019 12.
Article in English | MEDLINE | ID: mdl-31847047

ABSTRACT

Dizziness and vertigo are symptoms that commonly lead patients to seek neurologic or emergency care. Because symptoms are often vague and imprecise, a systematic approach is essential. By categorizing vestibular disorders based on the timing, triggers, and duration of symptoms, as well as emphasizing focused ocular motor and vestibular examinations, the majority of vestibular diagnoses can be made at the bedside. This paper will discuss the pearls and pitfalls in the history and examination of the most common acute, episodic, and chronic vestibular disorders.


Subject(s)
Practice Guidelines as Topic , Vestibular Diseases/diagnosis , Humans
17.
Semin Neurol ; 39(1): 53-60, 2019 02.
Article in English | MEDLINE | ID: mdl-30743292

ABSTRACT

Normal vision requires coordination of precisely controlled and coordinated eye movements and normal function of a large cortical and subcortical sensory network. Given the required precision of the system and wide anatomic distribution of the motor and sensory visual systems, vision can be disrupted by a variety of central and peripheral nervous system disorders. While many of these may be relatively benign or have no proven therapy, several may be isolated presentations or harbingers of more serious neurologic conditions. Both monocular and binocular vision losses may be isolated presentations of stroke or its equivalent. Other etiologies of monocular vision loss may represent the initial presentation of potentially disabling conditions. Binocular diplopia, caused by impaired movement of one or both eyes, may represent a condition with no acute therapy and a benign natural history, or a progressive potentially life-threatening syndrome. Most people are heavily reliant upon vision, so that even a subtle change in vision due to disturbed afferent or efferent pathways is invariably noticed, and presentation to the emergency department for eye symptoms is common. The accurate evaluation of these patients in the acute setting is essential to identify the patients requiring immediate testing or treatment.


Subject(s)
Neurologists/psychology , Vision Disorders/diagnosis , Vision Disorders/therapy , Acute Disease , Emergency Service, Hospital , Humans , Neurologists/standards
18.
J Neurol Phys Ther ; 43 Suppl 2: S27-S30, 2019 04.
Article in English | MEDLINE | ID: mdl-30883490

ABSTRACT

BACKGROUND AND PURPOSE: Both central (eg, brain stem, cerebellum) and peripheral (eg, vestibular, fourth cranial nerve palsy) etiologies can cause a vertical misalignment between the eyes with a resultant vertical diplopia. A vertical binocular misalignment may be due to a skew deviation, which is a nonparalytic vertical ocular misalignment due to roll plane imbalance in the graviceptive pathways. A skew deviation may be 1 component of the ocular tilt reaction. The purposes of this article are (1) to understand the pathophysiology of a skew deviation/ocular tilt reaction and (2) to be familiar with the examination techniques used to diagnose a skew and to differentiate it from mimics such as a fourth cranial nerve palsy. SUMMARY OF KEY POINTS: The presence of a skew deviation usually indicates a brain stem or cerebellar localization. Vertical ocular misalignment is easily missed when observing the resting eye position alone. RECOMMENDATIONS FOR CLINICAL PRACTICE: Physical therapists treating patients with vestibular pathology from central or peripheral causes should screen for vertical binocular disorders.


Subject(s)
Dizziness/diagnosis , Eye Movements/physiology , Vestibule, Labyrinth/physiopathology , Dizziness/physiopathology , Humans , Vestibular Function Tests
19.
Appl Microbiol Biotechnol ; 102(3): 1045-1054, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29204900

ABSTRACT

Recombinant adeno-associated virus (rAAV) vectors are increasingly popular tools for gene therapy applications. Their non-pathogenic status, low inflammatory potential, availability of viral serotypes with different tissue tropisms, and prospective long-lasting gene expression are important attributes that make rAAVs safe and efficient therapeutic options. Over the last three decades, several groups have engineered recombinant AAV-producing platforms, yielding high titers of transducing vector particles. Current specific productivity yields from different platforms range from 103 to 105 vector genomes (vg) per cell, and there is an ongoing effort to improve vector yields in order to satisfy high product demands required for clinical trials and future commercialization.Crucial aspects of vector production include the molecular design of the rAAV-producing host cell line along with the design of AAV genes, promoters, and regulatory elements. Appropriately, configuring and balancing the expression of these elements not only contributes toward high productivity, it also improves process robustness and product quality. In this mini-review, the rational design of rAAV-producing expression systems is discussed, with special attention to molecular strategies that contribute to high-yielding, biomanufacturing-amenable rAAV production processes. Details on molecular optimization from four rAAV expression systems are covered: adenovirus, herpesvirus, and baculovirus complementation systems, as well as a recently explored yeast expression system.


Subject(s)
Dependovirus/genetics , Genetic Vectors , Virus Cultivation , Adenoviridae/genetics , Animals , Baculoviridae/genetics , Cell Line , Genetic Therapy , Herpesviridae/genetics , Promoter Regions, Genetic , Viral Tropism , Yeasts/genetics
20.
Dermatol Surg ; 44(6): 865-869, 2018 Jun.
Article in English | MEDLINE | ID: mdl-29381548

ABSTRACT

BACKGROUND: Effective treatment of keloids is challenging because the recurrence rate after surgical excision is high. Data on the best treatment practices are lacking. OBJECTIVE: To investigate the recurrence rate after surgical excision of earlobe keloids based on a postoperative intralesional corticosteroid injection protocol. MATERIALS AND METHODS: Retrospective chart review was performed from January 1, 2005, to March 31, 2016, of patients who had excision of ear keloids within the departments of dermatology, otorhinolaryngology, and plastic surgery. The number of postoperative injections was recorded, recurrence was reported by the patient, and the efficacy of an injection protocol was evaluated. RESULTS: There were 277 charts reviewed. Appropriate data were available for 184 patients. A statistically significant difference was found with recurrence associated with a lower number of injections (p < .001). Keloids were more likely to recur if they were not treated with a planned serial injection protocol (p < .001) or if they were treated outside the department of dermatology (p < .001). CONCLUSION: Intralesional corticosteroid injection after surgical excision of earlobe keloids statistically minimizes the risk of recurrence.


Subject(s)
Ear, External/surgery , Glucocorticoids/administration & dosage , Keloid/surgery , Postoperative Care , Adolescent , Adult , Child , Female , Follow-Up Studies , Humans , Injections, Intralesional/methods , Male , Recurrence , Retrospective Studies , Treatment Outcome
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