-
Orphanet Journal of Rare Diseases Jun 2024The low prevalence of rare diseases poses a significant challenge in advancing their understanding. This study aims to delineate the clinical and genetic characteristics...
BACKGROUND
The low prevalence of rare diseases poses a significant challenge in advancing their understanding. This study aims to delineate the clinical and genetic characteristics of patients with rare eye diseases (RED) enrolled in the Spanish Rare Diseases Patient Registry.
METHODS
A total of 864 patients from the registry database were included. Diseases were categorized into inherited retinal dystrophies (n=688); anterior segment diseases (n=48); congenital malformations (n=27); and syndromic diseases with ocular involvement including muscular (n=46), neurological (n=34), or metabolic (n=13); inflammatory diseases (n=4); and tumors (n=4). Data on visual acuity (VA) and/or visual field (VF), symptoms and signs, concurrent diseases in syndromic cases, age of onset and at diagnosis, affected genes, disability rating, inability to work and dependency grade recognition were collected.
RESULTS
A mean diagnostic delay of 7 years from symptom onset was observed. Commonly reported symptoms included photophobia, night blindness, and progressive vision loss (≥57% of patients). Cataract was the most prevalent secondary disease (46%), with pseudophakia being the most common ocular surgery (26%). Hearing loss and cardiovascular diseases were the most prevalent concurrent systemic diseases (≥13%). Certificates of disability, incapacity for work, and dependency were held by 87%, 42%, and 19% of patients, respectively. Among the 719 patients with available VA data, 193 (27%) were blind, and 188 (26%) had moderate to severe visual impairment. Over half of the patients (54%) exhibited VF defects, and 216 (25%) had concentric contraction ≤5° or abolished VF. Most had genetic diseases with autosomal recessive (55%), autosomal dominant (30%), X-linked (9%), and mitochondrial (6%) patterns. One patient had mutations in both recessive USH2A and dominant RHO genes simultaneously. Of the 656 patients (75.7%) who underwent genetic testing, only 461 (70.3%) received a positive result (pathogenic or likely pathogenic mutations explaining the phenotype). We found 62 new gene variants related to RED not previously reported in databases of genetic variants related to specific phenotypes.
CONCLUSIONS
This study delineates the clinical and genotypic profiles of RED in Spain. Genetic diseases, particularly retinal disorders, predominate, but a significant proportion of affected patients remain genetically undiagnosed, hindering potential gene therapy endeavors. Despite notable improvements in reducing diagnosis delays, it is still remarkable. RED frequently lead to disability and blindness among young populations.
Topics: Humans; Male; Female; Eye Diseases; Registries; Spain; Adult; Rare Diseases; Middle Aged; Adolescent; Child; Young Adult; Child, Preschool; Aged; Infant; Visual Acuity; Retinal Dystrophies
PubMed: 38872169
DOI: 10.1186/s13023-024-03242-6 -
Clinical Practice and Cases in... May 2024A 52-year-old female presented to the emergency department with four days of right periorbital pain, ipsilateral temporal headache, diplopia, and photophobia. Physical...
CASE PRESENTATION
A 52-year-old female presented to the emergency department with four days of right periorbital pain, ipsilateral temporal headache, diplopia, and photophobia. Physical examination of the right eye revealed painful ophthalmoplegia, cranial nerves III and VI paresis, increased intraocular pressure, and mild proptosis. Magnetic resonance venogram and magnetic resonance imaging orbits with contrast demonstrated an abnormal signal surrounding the right cavernous sinus/petrous apex. Tolosa-Hunt syndrome (THS) was diagnosed. Per neurology recommendations, the patient was placed on a steroid regimen over the course of three weeks. She was discharged on hospital day nine following resolution of symptoms. She had no recurrence of symptoms or residual deficits noted at her two-week follow-up appointment.
DISCUSSION
With an estimated annual incidence of one case per million, THS is a sinister etiology of unilateral headache, painful ophthalmoplegia, and oculomotor palsy. Tolosa-Hunt syndrome is caused by granulomatous inflammation in the cavernous sinus and is highly responsive to corticosteroids. Magnetic resonance imaging studies of the cavernous sinus and orbital apex are highly sensitive for THS and characteristically show enlargement and focal-enhancing masses within the affected cavernous sinus.
PubMed: 38869347
DOI: 10.5811/cpcem.2582 -
Cureus Apr 2024Benign intracranial hypertension (BIH) in children is recognized as elevated intracranial pressure without hydrocephalus or intracranial mass. It manifests differently...
Benign intracranial hypertension (BIH) in children is recognized as elevated intracranial pressure without hydrocephalus or intracranial mass. It manifests differently in adults, with no apparent predilection for sex or weight. Headache, papilledema, and possibly sixth nerve palsy with visual field defects are the typical symptoms of this syndrome. Vitamin A toxicity is a rare cause of BIH. We report the case of a previously healthy 13-year-old girl presenting with photophobia, a frontal headache, and vomiting. She had bilateral papilledema discovered by fundoscopy. Both magnetic resonance imaging and brain CT were normal. At admission, a lumbar puncture (LP) revealed an opening pressure of 26 cm HO with normal cerebrospinal fluid (CSF) analysis. The diagnosis of BIH was established, and treatment with acetazolamide was started, with good clinical results. Regular eye evaluations showed a regression of papilledema. Elevated serum vitamin A levels were the only positive findings. Within two weeks, the patient was discharged without any symptoms. This study aims to attract the attention of clinicians to the importance of evaluating vitamin A toxicity in the context of papilledema and oculomotor problems in a child who has undergone normal neuroradiological investigations.
PubMed: 38817456
DOI: 10.7759/cureus.59401 -
Cureus Apr 2024Meningitis is the inflammation of meninges either septic or aseptic depending on the source of infection. Typical signs and symptoms of meningitis in children...
Meningitis is the inflammation of meninges either septic or aseptic depending on the source of infection. Typical signs and symptoms of meningitis in children include fever, headache, neck stiffness, nuchal rigidity represented by positive Kernig and Brudzinski signs, photophobia, nausea, vomiting, confusion, lethargy, and irritability. Bacterial meningitis is commonly caused by in children over the age of three months. Although there has been a decline in infections due to the introduction of the pneumococcal conjugate and pneumococcal polysaccharide vaccines, there are still reported cases of invasive pneumococcal infections mostly with non-vaccine serotypes. We report a fully immunized six-year-old male patient with a presentation of classic meningitis signs and symptoms who developed rapid progression of disease including sudden and dramatic change in physical exam and subsequent respiratory depression within 12 hours of admission. Our patient had a history of extensive traumatic facial bone fractures six months prior. Our case demonstrates a unique presentation of rapidly progressing pneumococcal meningitis due to a suspected complication of septic thrombophlebitis and subsequent brain herniation in a fully immunized patient six months after a severe traumatic facial injury.
PubMed: 38807822
DOI: 10.7759/cureus.59204 -
BMC Neurology May 2024Surveys using questionnaires to collect epidemiologic data may be subject to misclassification. Here, we analyzed a headache questionnaire to evaluate which questions...
A study to investigate the prevalence of headache disorders and migraine conducted using medical claims data and linked results from online surveys: post-hoc analysis of other headache disorders.
BACKGROUND
Surveys using questionnaires to collect epidemiologic data may be subject to misclassification. Here, we analyzed a headache questionnaire to evaluate which questions led to a classification other than migraine.
METHODS
Anonymized surveys coupled with medical claims data from individuals 19-74 years old were obtained from DeSC Healthcare Inc. to examine proportions of patients with primary headache disorders (i.e.; migraine, tension-type headache, cluster headache, and "other headache disorders"). Six criteria that determined migraine were used to explore how people with other headache disorders responded to these questions.
RESULTS
Among the 21480 respondents, 7331 (34.0%) reported having headaches. 691 (3.2%) respondents reported migraine, 1441 (6.7%) had tension-type headache, 21 (0.1%) had cluster headache, and 5208 (24.2%) reported other headache disorders. Responses of participants with other headache disorders were analyzed, and the top 3 criteria combined with "Symptoms associated with headache" were "Site of pain" (7.3%), "Headache changes in severity during daily activities" (6.4%), and the 3 criteria combined (8.8%). The symptoms associated with headache were "Stiff shoulders" (13.6%), "Stiff neck" (9.4%), or "Nausea or vomiting" (8.7%), Photophobia" (3.3%) and "Phonophobia" (2.5%).
CONCLUSIONS
Prevalence of migraine as diagnosed by questionnaire was much lower than expected while the prevalence of "other headache" was higher than expected. We believe the reason for this observation was due to misclassification, and resulted from the failure of the questionnaire to identify some features of migraine that would have been revealed by clinical history taking. Questionnaires should, therefore, be carefully designed, and doctors should be educated, on how to ask questions and record information when conducting semi-structured interviews with patients, to obtain more precise information about their symptoms, including photophobia and phonophobia.
Topics: Humans; Middle Aged; Adult; Male; Female; Prevalence; Migraine Disorders; Aged; Surveys and Questionnaires; Young Adult; Headache Disorders; Internet; Health Surveys
PubMed: 38796414
DOI: 10.1186/s12883-024-03675-3 -
American Journal of Ophthalmology May 2024To present the clinical characteristics, retinal features, natural history, and genetics of RPGRIP1-Associated Early Onset Severe Retinal Dystrophy (EOSRD)/Leber...
PURPOSE
To present the clinical characteristics, retinal features, natural history, and genetics of RPGRIP1-Associated Early Onset Severe Retinal Dystrophy (EOSRD)/Leber Congenital Amaurosis (LCA).
DESIGN
Retrospective case series.
METHODS
Review of clinical notes, multi-modal retinal imaging, and molecular diagnosis of 18 patients (17 families) with EOSRD/LCA and disease-causing variants in RPGRIP1.
RESULTS
The mean age of visual symptoms onset was 0.87 ± 1 year (birth-3 years) and the mean age at baseline visit was 11.4 ± 10.2 years (1-39 years). At the baseline visit, 44% of patients were legally blind (range= 2-39 years) and there was no significant association found between age and best corrected visual acuity (BCVA) in cross sectional analysis. Retinal evaluation showed an abolished electroretinogram or a cone-rod dystrophy pattern, none or minimal pigment deposits, a hyperautofluorescent ring at the posterior pole, and a largely preserved central macular architecture, with retained outer nuclear layer and ellipsoid zone island into adulthood. Eleven variants (48%) were previously unreported, and 13 families (76%) had a double null genotype (DN). Twelve patients (67%) had follow up assessments over a 15.7 ± 9.5 year period. The rate of BCVA decline was 0.02 LogMAR (1 letter)/year.
CONCLUSIONS
RPGRIP1-EOSRD/LCA often presents at birth or early infancy, with nystagmus, decreased VA, hyperopia, and photophobia. Patients with a DN genotype may develop symptoms earlier and have worse vision. Multimodal imaging may show a hyperautofluorescent posterior pole ring, and relatively preserved central macular architecture, suggesting that the condition is a promising candidate for gene supplementation.
PubMed: 38768745
DOI: 10.1016/j.ajo.2024.05.007 -
Frontiers in Neurology 2024Calcitonin gene-related peptide (CGRP) plays an important role in cerebral vasodilation, so here we aim to quantify the impact of CGRP monoclonal antibody (mAb) therapy...
INTRODUCTION
Calcitonin gene-related peptide (CGRP) plays an important role in cerebral vasodilation, so here we aim to quantify the impact of CGRP monoclonal antibody (mAb) therapy on cerebral hemodynamics.
METHODS
In 23 patients with chronic and episodic migraine, cerebral hemodynamic monitoring was performed (1) prior to and (2) 3-months into CGRP-mAb therapy. Transcranial Doppler monitored cerebral blood flow velocity (CBFv) in the middle cerebral artery (MCA) and posterior cerebral artery (PCA), from which cerebrovascular reactivity (CVR) and cerebral autoregulation (CA; ) were calculated.
RESULTS
CA was similar off and on treatment, in the MCA ( = 0.42) and PCA ( = 0.72). CVR was also unaffected by treatment, in the MCA ( = 0.38) and PCA ( = 0.92). CBFv and blood pressure were also unaffected. The subgroup of clinical responders (>50% reduction in migraine frequency) exhibited a small reduction in MCA-CBFv (6.0 cm/s; IQR: 1.1-12.4; = 0.007) and PCA-CBFv (8.9 cm/s; IQR: 6.9-10.3; = 0.04).
DISCUSSION
Dynamic measures of cerebrovascular physiology were preserved after 3 months of CGRP-mAb therapy, but a small reduction in CBFv was observed in patients who responded to treatment. Subgroup findings should be interpreted cautiously, but further investigation may clarify if CBFv is dependent on the degree of CGRP inhibition or may serve as a biomarker of drug sensitivity.
PubMed: 38746660
DOI: 10.3389/fneur.2024.1399792 -
Journal of Neurosciences in Rural... 2024Spontaneous intracranial hypotension (SIH) is a condition characterized by orthostatic headache associated with nausea, vomiting, tinnitus, vertigo, hypoacusis, neck...
Spontaneous intracranial hypotension (SIH) is a condition characterized by orthostatic headache associated with nausea, vomiting, tinnitus, vertigo, hypoacusis, neck pain/stiffness, and photophobia. Usual treatment includes bed rest, hydration, caffeine, analgesics, epidural blood patch, steroids, fibrin glue (N-butyl-cyanoacrylate), and surgical repair. In this series, we report two cases, who presented to us with features of SIH and were managed successfully with sphenopalatine ganglion block. This is a novel modality of management of SIH and has not been reported before.
PubMed: 38746504
DOI: 10.25259/JNRP_30_2024 -
Cureus Apr 2024Aseptic meningitis is a rare but serious complication of treatment with intravenous immunoglobulin (IVIG) and often mimics meningitis of infectious etiology which poses...
Aseptic meningitis is a rare but serious complication of treatment with intravenous immunoglobulin (IVIG) and often mimics meningitis of infectious etiology which poses a challenge for timely diagnosis. Although there are published recommendations on the management of IVIG-induced complications, there are no clear guidelines on the continuation of IVIG use after resolution of aseptic meningitis. We present a case of IVIG-induced aseptic meningitis in a patient with a history of refractory dermatomyositis who had been treated with immunosuppressive therapy and IVIG infusions for over a year. The patient developed intense head and neck pain with associated photophobia 24 hours after the most recent IVIG infusion. The patient was managed with supportive care consisting of intravenous fluids and analgesics. The patient's aseptic meningitis resolved without neurological complications. Ultimately, the patient was restarted on IVIG due to the recurrence of weakness from dermatomyositis. The patient tolerated re-initiation of IVIG without recurrence of IVIG-induced complications. This case highlights the importance of considering IVIG-induced aseptic meningitis as a differential diagnosis in evaluating patients with non-infectious meningitis even after regular IVIG infusions. This case also demonstrates that it is safe to reinitiate IVIG after the resolution of IVIG-induced aseptic meningitis.
PubMed: 38745808
DOI: 10.7759/cureus.58242 -
Case Reports in Women's Health Jun 2024NMDA-R encephalitis is an autoimmune encephalitis that is known to be associated with ovarian teratomas. Eighty to 100 % of patients initially present with...
NMDA-R encephalitis is an autoimmune encephalitis that is known to be associated with ovarian teratomas. Eighty to 100 % of patients initially present with neuropsychiatric symptoms. Early recognition and intervention are critical to management and prognosis. This case demonstrates non-specific presenting symptoms of NMDA-R encephalitis. A 32-year-old woman presented to the emergency room with headache, nausea, vomiting, and photophobia. She was discharged with probable aseptic meningitis. Eight days later, she represented with delusional thought content, perseverative speech, and bizarre behavior. Cerebrospinal fluid studies showed elevated protein and mild pleocytosis. A computed tomography scan with contrast showed a 35-mm complex cystic lesion in the right adnexa, which was resected. Confirmatory pathology showed a mature cystic teratoma. Paraneoplastic panel later resulted positive for NMDA-R encephalitis. The patient was treated with methylprednisolone, IVIG, plasmapheresis, and rituximab. The clinical course was complicated by a hypersensitivity reaction to rituximab, non-convulsive status epilepticus requiring intubation, dysphagia requiring a PEG placement, a rectal ulcer causing acute blood loss anemia requiring multiple blood transfusions, bilateral hearing loss, and a left lung pneumothorax. The patient's mood, cognition, and motor function were favorably improving 19 months after diagnosis. This case illustrates presenting signs of NMDA-R encephalitis in a young woman as headache and altered mental status followed by psychosis and epilepsy. Treatment should involve a multidisciplinary team and be individualized and escalated in patients with worsening clinical status refractory to first-line therapy. Further research is warranted to understand the optimal treatment strategy for this disease.
PubMed: 38737718
DOI: 10.1016/j.crwh.2024.e00612