Classic Triad Research Articles

Miller Fisher syndrome: an updated narrative review.

Miller Fisher syndrome (MFS) is considered a rare variant of Guillain-Barré syndrome (GBS), a group of acute-onset immune-mediated neuropathies characterized by the classic triad of ataxia, areflexia, and ophthalmoparesis. The present review aimed to provide a detailed and updated profile of all aspects of the syndrome through a collection of published articles on the subject, ranging from the initial description to recent developments related to COVID-19. We searched PubMed, Scopus, EMBASE, and Web of Science databases and gray literature, including references from the identified studies, review studies, and conference abstracts on this topic. We used all MeSH terms pertaining to "Miller Fisher syndrome," "Miller Fisher," "Fisher syndrome," and "anti-GQ1b antibody." An extensive bibliography was researched and summarized in the review from an initial profile of MFS since its description to the recent accounts of diagnosis in COVID-19 patients. MFS is an immune-mediated disease with onset most frequently following infection. Anti-ganglioside GQ1b antibodies, detected in ~85% of patients, play a role in the pathogenesis of the syndrome. There are usually no abnormalities in MFS through routine neuroimaging. In rare cases, neuroimaging shows nerve root enhancement and signs of the involvement of the central nervous system. The most consistent electrophysiological findings in MFS are reduced sensory nerve action potentials and absent H reflexes. Although MFS is generally self-limited and has excellent prognosis, rare recurrent forms have been documented. This article gives an updated narrative review of MFS with special emphasis on clinical characteristics, neurophysiology, treatment, and prognosis of MFS patients.

Risk Factors and Predictors of Occlusion of Stent of Trans Jugular Intrahepatic Porto-Systemic Shunt (TIPSS) in Egyptian Patients with Primary Budd Chiari Syndrome: A Single Center Experience

Background Budd–Chiari syndrome is a heterogeneous group of disorders characterized by hepatic venous outflow obstruction at the level of the hepatic venules, the large hepatic veins, the inferior vena cava till its junction with the right atrium. The classic triad of abdominal pain, ascites, and hepatomegaly is observed in the vast majority of patients with Budd-Chiari syndrome. The diagnosis of BCS is made by clinical presentation and confirmatory investigations. Standard laboratory investigations are rarely helpful in establishing the diagnosis, because abnormal liver function tests are not specific for BCS, real time Gray-scale sonography combined with colour flow is considered by some to be the initial imaging technique. The recommended stepwise therapeutic algorithm of BCS is mainly by medical treatment with anticoagulation, angioplasty with or without stenting, TIPS of surgical shunting and liver transplantation if indicated. TIPS is a common teqnique used in BCS and TIPS stent occlusion is major complication. Objectives To identify the possible risk factors and predictors of stent occlusion in primary BCS patients who underwent TIPSS. Patients and Methods The studied patients were selected from patients presented to Budd Chiari outpatient clinic. Tropical medicine department in Ain Shams University hospitals. total number of cases during the study period was 76 cases fulfilling the inclusion criteria, they were divided in 2 groups according to patency of TIPS stent and comparing both groups regarding their pre and post TIPS data. Results The mean age of the patients was (29.29 ± 7.92) with female predominance. FVLM (69.7%) & MTHFRD (67.1%) were the most common causes of BCS in the studied patients. positive and higher CRP results were found in the occluded stent patients than patent groups. also, higher TLC levels were found in the occluded TIPS stent patients. Conclusion Identifying these risk factors may help predict the outcome of TIPS stent patency.

Polymorphism Detection of VKORC1 (Vitamin K Epoxide Reductase Complex, Subunit 1) Gene for Warfarin Dose Adjustment in Egyptian Patients with Budd Chiari and/or Portal Vein Thrombosis: A Single Center Experience

Background Budd–Chiari syndrome is a heterogeneous group of disorders characterized by hepatic venous outflow obstruction at the level of the hepatic venules, the large hepatic veins, the inferior vena cava till its junction with the right atrium. The classic triad of abdominal pain, ascites, and hepatomegaly is observed in the vast majority of patients with Budd-Chiari syndrome, but it is nonspecific. Warfarin was introduced into clinical practice in the 1950s, and has been the most widely prescribed oral anti-coagulant for prevention and treatment of thrombotic diseases despite its significant side effects as (bleeding tendency, drug drug interaction). Vitamin K epoxide reductase complex subunit1 (VKORC1), a membrane protein located in hepatocytes, has an important role in the anabolism of vitamin K, which is essential for blood coagulation. Objectives The aim beyond this study is to evaluate effect of the allelic frequency of the VKORC1 (G1639A) polymorphic genes by real time PCR on response of Egyptian patients with Budd–Chiari syndrome or PVT to Warfarin. Patients and Methods The studied patients were selected from patients presented to Budd chiari study group clinic.tropical medicine department in Ain Shams University hospitals. Within 6 months from july 2020 to December 2020, total number of cases during the study period was 50 cases fulfilling the inclusion criteria Results The mean age of the patients was (32.40 ± 9.69) slightly more common in males. The chronic presentation represented 60% of the patients and the acute represented 32%.The most common cause of budd chiarri syndrome was MTHFRD (52%) followed by FVLM (36%) then Primary ant phospholipid antibody syndrome (26%). Patients with the −1639 promoter polymorphism GG genotype had lower dose requirements, whereas the AG/AA genotypes had higher dose. Conclusion Identifying these polymorphisms in patients prior to starting the therapy may help clinicians choose the appropriate warfarin dose & decrease its adverse effects.

Novel association of Dandy-Walker malformation with CAPN15 variants expands the phenotype of oculogastrointestinal neurodevelopmental syndrome.

Oculogastrointestinal neurodevelopmental syndrome has been described in seven previously published individuals who harbor biallelic pathogenic variants in the CAPN15 gene. Biallelic missense variants have been reported to demonstrate a phenotype of eye abnormalities and developmental delay, while biallelic loss of function variants exhibit phenotypes including microcephaly and craniofacial abnormalities, cardiac and genitourinary malformations, and abnormal neurologic activity. We report six individuals from three unrelated families harboring biallelic deleterious variants in CAPN15 with phenotypes overlapping those previously described for this disorder. Of the individuals affected, four demonstrate radiographic evidence of the classical triad of Dandy-Walker malformation including hypoplastic vermis, fourth ventricle enlargement, and torcular elevation. Cerebellar anomalies have not been previously reported in association with CAPN15-related disease. Here, we present three unrelated families with findings consistent with oculogastrointestinal neurodevelopmental syndrome and cerebellar pathology including Dandy-Walker malformation. To corroborate these novel clinical findings, we present supporting data from the mouse model suggesting an important role for this protein in normal cerebellar development. Our findings add six molecularly confirmed cases to the literature and additionally establish a new association of Dandy-Walker malformation with biallelic CAPN15 variants, thereby expanding the neurologic spectrum among patients affected by CAPN15-related disease.

A Rare Case of Dyskeratosis Congenita: A Case Report from Tribal State of Arunachal Pradesh, Northeast India

Dyskeratosis congenita is a rare genodermatosis, which is characterized by triad of skin pigmentation, nail dystrophy and leukoplakic lesion in the oral cavity. The purpose of reporting this case with review of recent literature is to create better awareness about the multisystem manifestations of this fatal condition that can aid clinicians in early diagnosis. A case of 12 year old female is reported presenting with classical triad of lesions with briefly review of literature.

Pheochromocytoma in a Pediatric Patient: A Case Report

A pheochromocytoma is a rare catecholamine secreting neuroendocrine tumor, originating within the adrenal medulla. Most cases present with a hypertensive crisis and a classic triad of headaches, sweating, and palpitations. A positive prognosis is projected for patients after operative removal of the tumor. Early detection of this tumor is crucial as it can be fatal if left untreated. Clinical signs and symptoms, diagnostic criteria, and imaging appearances are described to assist in this case of a pheochromocytoma, detected in a pediatric patient. A 16-year-old female presented to the hospital with symptoms of chest pain, hypertensive crisis, and vision loss. A renal sonogram was performed and revealed a left sided adrenal mass. Correlating the sonogram with magnetic resonance imaging (MRI), tumor markers, and clinical presentation confirmed this pathology as a benign pheochromocytoma in a pediatric patient with hypertension. Medical and surgical intervention was provided to yeild a positive outcome for this patient.

Managing Idiopathic Normal Pressure Hydrocephalus: Need for a Change of Mindset

Idiopathic normal pressure hydrocephalus (iNPH) refers to a complex brain disorder characterized by ventricular enlargement and the classic Hakim's triad of gait and balance difficulties, urinary incontinence, and cognitive impairment. It predominantly affects older patients in the absence of an identified cause. As the elderly population continues to increase, iNPH becomes a growing concern in the complex spectrum of neuro-geriatric care, with significant socio-economic implications. However, unlike other well-structured management approaches for neurodegenerative disorders, the management of iNPH remains largely uncodified, leading to suboptimal care in many cases. In this article, we highlighted the challenges of current practice and identify key points for an optimal structuration of care for iNPH. Adopting a global approach to iNPH could facilitate a progressive shift in mindset, moving away from solely aiming to cure an isolated neurological disease with uncertain outcomes to providing comprehensive care that focuses on improving the daily life of frail patients with complex neurodegenerative burdens, using tailored goals.

Aicardi Syndrome Is a Genetically Heterogeneous Disorder.

Aicardi Syndrome (AIC) is a rare neurodevelopmental disorder recognized by the classical triad of agenesis of the corpus callosum, chorioretinal lacunae and infantile epileptic spasms syndrome. The diagnostic criteria of AIC were revised in 2005 to include additional phenotypes that are frequently observed in this patient group. AIC has been traditionally considered as X-linked and male lethal because it almost exclusively affects females. Despite numerous genetic and genomic investigations on AIC, a unifying X-linked cause has not been identified. Here, we performed exome and genome sequencing of 10 females with AIC or suspected AIC based on current criteria. We identified a unique de novo variant, each in different genes: KMT2B, SLF1, SMARCB1, SZT2 and WNT8B, in five of these females. Notably, genomic analyses of coding and non-coding single nucleotide variants, short tandem repeats and structural variation highlighted a distinct lack of X-linked candidate genes. We assessed the likely pathogenicity of our candidate autosomal variants using the TOPflash assay for WNT8B and morpholino knockdown in zebrafish (Danio rerio) embryos for other candidates. We show expression of Wnt8b and Slf1 are restricted to clinically relevant cortical tissues during mouse development. Our findings suggest that AIC is genetically heterogeneous with implicated genes converging on molecular pathways central to cortical development.

Perforative duodenal ulcer in a patient in the acute period of ischemic stroke. Case report

Perforated duodenal ulcer is a common pathology with fairly high postoperative mortality, especially in late diagnosis. In some cases, timely diagnosis of a perforative ulcer may be difficult and the results of the survey may be contradictory. The classical triad of clinical signs of perforative ulcers is not always observed in patients, sometimes the clinical picture is so unclear that the final diagnosis can only be made intraoperative. The article presents an analysis of the clinical case of difficult diagnosis and treatment of perforative duodenal ulcer in a patient in an acute period of ischemic stroke. In addition, the patient had severe concomitant somatic pathology with a high risk of systemic thromboembolism and at the same time a high risk of bleeding.

A Rare Case of Horner's Syndrome after Neck Dissection Operation

The classic triad of ipsilateral palpebral ptosis, pupillary miosis, and facial anhidrosis defines Horner's syndrome, which results from cervical sympathetic chain damage. This is an uncommon complication of neck surgery like thyroidectomy and neck dissection. A fifty-two-year-old male patient presented with papillary thyroid carcinoma with lymph nodes metastases, underwent total thyroidectomy with central and left lateral modified radical neck dissection. One day after the operation, the patient presented with signs of Horner's syndrome.

Olfactory function in Susac syndrome

ObjectivesSusac syndrome is a rare autoimmune endotheliopathy involving the brain, retina, and inner ear. Olfactory dysfunction is a common early manifestation of several central nervous system diseases, including neurodegenerative diseases and autoimmune-mediated diseases such as Multiple Sclerosis. While the literature is abundant about the Susac syndrome classic triad of encephalopathy, branch retinal artery occlusion, and low-frequency sensorineural hearing loss, little is known about the extent of olfactory sense involvement. MethodsUsing the Sniffin' Sticks test, this study evaluated olfactory function (identification and threshold) in ten recovering Susac syndrome patients under our clinic surveillance with a median of 3.1 (SD=1.53) years post-disease onset. Resultsolfactory assessment by threshold and odor identification were within the normal range. No differences between recovering Susac syndrome patients to standard norms of odor identification and threshold were found. ConclusionsOur findings do not support olfactory dysfunction in Susac syndrome and thereby, do not support olfactory assessment as a reliable biomarker for this condition.

Melkersson-Rosenthal Syndrome and Migraine: A New Phenotype Associated with SCN1A Variants?

Peripheral facial palsy rarely occurs as part of Melkersson-Rosenthal syndrome (MRS), which is characterized by the classical triad of tongue cheilitis, recurrent episodes of orofacial swelling, and palsy. MRS is a disorder with variable expressivity and clinical as well as genetic heterogeneity; however, the causative gene remains to be identified. Migraine is a common neurological disorder, presenting with or without aura, which may be associated with neurological symptoms. The classical example of monogenic migraine is familial hemiplegic migraine (FHM), which has phenotypic variability in carriers of variants in the same gene or even carriers of the same variant. We present a family in which two sisters displayed recurrent migraines, one of which presented recurrent facial palsy and had clinical diagnosis of MRS. We performed WES and Sanger sequencing for segregation analysis in the available family members. We identified a c.3521C>G missense heterozygous variant in SCN1A carried only by the affected sister. Variants in the SCN1A gene can cause a spectrum of early-onset epileptic encephalopathies, in addition to FHM; therefore, our finding reasonably explains the proband phenotype, in which the main symptom was recurrent facial palsy. This report also adds knowledge to the clinical spectrum of SCN1A alterations and suggests a potential overlap between MRS and FHM.

Serologic Testing for Rocky Mountain Spotted Fever in a Low-Incidence Region.

Tick-borne diseases have grown in incidence over recent decades. As a result, diagnostic testing has become more common, often performed as broad antibody-based panels for multiple tick-transmitted pathogens. Rocky Mountain spotted fever (RMSF) is rare in our region yet may cause severe morbidity, leading to diagnostic screening in low-risk patients. We sought to describe trends in RMSF diagnostic testing, rate of IgG seropositivity, and clinical features of those tested. We performed a retrospective chart review of patients ≤21 years old undergoing testing for RMSF and/or with an ICD-9/10 code for RMSF. Patients were categorized by infection likelihood based on clinical and laboratory criteria adapted from Centers for Disease Control and Prevention's (CDC) case definition of spotted fever rickettsioses. Clinical data were collected and analyzed with descriptive statistics. One hundred and seventy patients were included. 5.8% met CDC criteria for rickettsial infection, 6.5% had an elevated IgG titer but lacked suggestive symptoms, and 87.6% had a negative IgG titer. Many patients tested were unlikely to have RMSF, including 50% lacking fever, 20% lacking any RMSF "classic triad" symptoms, 13% without acute illness, and 22% tested during months with low tick activity. Convalescent serology was performed in 7.6% of patients and none underwent Rickettsia rickettsii polymerase chain reaction (PCR) testing. Diagnostic testing was frequently performed in patients unlikely to have RMSF. We identified many opportunities for improving test utilization. Reserving testing for those with higher pretest probability, performing convalescent serology, and utilizing PCR may improve the accuracy of RMSF diagnosis and reduce clinical challenges stemming from inappropriate testing.

Anaesthesia Management of a Parturient with Klippel Feil Syndrome Undergoing Emergency Cesarean Section

Klippel Feil syndrome (KFS) is a rare autosomal genetic disorder comprising of classical triad of short neck, low hairline, and limited neck mobility. Parturient with KFS syndrome presents with difficult airway and needs individualized consideration for Anaesthesia. Management with Regional Anaesthesia has its pros and cons and can be considered in parturient with KFS as General Anaesthesia in pregnancy poses increased risk of aspiration, difficult mask ventilation and endotracheal intubation. We present a case of a 25-yr old parturient G3A2 with 34+4 weeks of gestation with KFS syndrome posted for emergency caesarean section managed successfully under spinal anaesthesia.

Pheochromocytoma: Clinical Experience From a Single Tertiary Care Center in India.

Pheochromocytoma is a catecholamine-secreting tumor arising from adrenomedullary chromaffin cells that has a varied clinical presentation. Identification of this tumor, which has episodic symptoms, is a diagnostic challenge for clinicians. Diagnosis at an appropriate time is important because it is associated with significant morbidity and mortality. This study aims to mitigate the limited availability of data in our geographical area. To assess the clinical, biochemical, and radiological features and outcomes of patients diagnosed with pheochromocytoma at our center. This is a retrospective study. Patients diagnosed with pheochromocytoma during 2015-2023 were included in the study. Clinical, biochemical, and radiological data were collected at presentation, post-surgery, discharge, and until the last follow-up; data were retrieved from hospital records. Statistical analysis was done using IBM Corp. Released 2011. IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp. This study included 19 patients, of whom 10 (52.6%) were female. The most common clinical presentation was a hypertensive crisis in patients with pre-existing hypertension (63.1%), followed by headache (47.3%). The classical triad of headache, palpitation, and sweating was seen in only three patients (15.7%). The mean tumor size was 5.01±2.06 cm, with a range of 2.5 to 12 cm. All patients underwent adrenalectomy; six patients (31.5%) had perioperative complications, with post-operative hypotension being the most common at 21% (n = 4), followed by an acute coronary event during alpha blockade in one patient (0.05%) and an intra-operative hypertensive crisis in one patient (5%). A biochemical remission rate post-surgery was achieved in 17 (89.47%) patients. Hypertensive crisis in patients with pre-existing hypertension was the predominant presenting feature in most of our patients. Female predominance was noted (52.3%) compared to males. Perioperative complications were observed in 31.5% of patients, with post-operative hypotension being the most common complication.

Multiple Pulmonary Emboli as a Primary Presentation of Renal Cell Carcinoma

A 57-year-old housewife presented with complaints of sudden onset of chest pain and dyspnea. Computed tomography angiography revealed saddle-shaped pulmonary emboli in the main pulmonary artery and its branches. Evaluation for the cause of pulmonary embolism revealed a heterogeneously enhancing lesion arising from the anterior aspect of the lower pole of the left kidney. She had no hematuria, flank pain, or any palpable abdominal mass. She underwent a left open radical nephrectomy with inferior vena cava thrombectomy. Given that only 10% of patients present with the classic triad, it is often difficult to diagnose renal cell carcinoma in the early stages. Therefore, a high index of suspicion in patients with atypical presentations can lead to an early diagnosis.

Asymptomatic Renal Cell Carcinoma Presenting as Clavicle Fracture

Abstract Renal cell carcinoma (RCC) accounts for 3% of all cancer cases. The classical triad of hematuria, loin pain, and mass per abdomen is rarely seen. RCC commonly metastasizes to the lungs, bones, and liver. Clavicle metastasis as the sole presentation of RCC is extremely rare. A 61-year-old man presented with pain and swelling over the left clavicle. Imaging revealed a lytic lesion with pathological fracture of the left clavicle, with a histopathological diagnosis of metastasis from clear cell RCC. Subsequent imaging of the abdomen revealed a right kidney mass. He underwent right partial nephrectomy and total left cleidectomy. At 30-month follow-up, he is free of disease with good limb function. Solitary skeletal metastasis from RCC is rare, of which clavicle metastasis as the initial presentation is extremely rare. The overall prognosis of metastatic RCC is poor, emphasizing the importance of identification of the pathological nature of the fracture, for early detection and prompt treatment of the primary tumor in its early stage, thereby improving the chances of overall survival.

Analysis of a series of Italian APECED patients with autoimmune hepatitis and gastro-enteropathies.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome is a rare monogenic disease determined by biallelic mutations in AIRE gene, which encodes a transcription factor essential for central immune tolerance. Classic diagnosis is determined by the presence of two of the main APECED clinical diseases: chronic mucocutaneous candidiasis, chronic hypoparathyroidism, and Addison's disease. Non-endocrine autoimmunity, involving the liver, intestine, eyes, and kidneys, is generally reported in a minority of European patients, while American APECED patients have a higher tendency of developing organ-specific non-endocrine manifestations early in life. This observation led to the revision of the diagnostic criteria to permit earlier diagnosis based on the appearance of one classic triad symptom or one non-classical manifestation at a young age in the presence of IFNωAbs or AIRE mutations (Ferre-Lionakis criteria). We analyzed the clinical, genetic, and autoantibody (Ab) profiles in a series of 14 pediatric Italian APECED patients with gastrointestinal manifestations (seven male and seven female patients). Ten patients presented hepatitis (APECED-associated hepatitis (APAH)), while seven were affected by constipation, diarrhea, and malabsorption. Four patients had developed APAH before classic triad symptoms. Based on the age of appearance of non-endocrine manifestations including APAH and gastro-enteropathy, the Ferre-Lionakis criteria would have allowed an expedited diagnosis in 11/14 patients. Abs to tryptophan hydroxylase (TPHAb) and hepatic aromatic l-amino acid decarboxylase (AADC) were significantly associated with APECED patients of the present series. Abs to cP4501A2 were detectable in the serum of 4/8 patients with APAH, and Abs to cP4502A6 were detectable in 3/8 patients. AADC Abs tested positive in 5/7 patients, which is indicative of gastrointestinal dysfunction in APECED and TPHAb in 5/7 patients with gastrointestinal dysfunction. IFNAb was significantly associated with the syndrome. Although Ferre-Lionakis expanded criteria applied to the American cohorts of APECED patients would require validation in independent large cohorts of European patients, the results of this study emphasize the importance to evaluate the presence and the age of appearance of APAH and autoimmune enteropathy even in European cohorts for an earlier APECED diagnosis. An earlier APECED diagnosis would also allow the prevention of episodes of life-threatening hypocalcemic seizures and adrenal crisis, which are the main manifestations of undiagnosed APECED.

Fat embolism syndrome with a typical manifestation on brain magnetic resonance imaging: a case report

Fat embolism (FE) occurs frequently after trauma, particularly the fracture of long bones in the lower extremities. FE syndrome (FES) is defined as the clinical symptoms and signs of organ dysfunction caused by the obstruction of capillaries by fat emboli and inflammatory reaction. Cerebral involvement, respiratory insufficiency, and petechial rash constitute classical triad. Brain magnetic resonance imaging (MRI) is a sensitive imaging technique for diagnosing cerebral involvement and severity of damage in FES. This study presents a case of FES that was diagnosed based on typical manifestation on brain MRI and treated conservatively without complications.

Professional and ethical approaches to characterize complications in elective spinal neurosurgery. Never events in lumbar discectomy

Any surgical intervention is associated with the possible development of complications. Surgical complications are traditionally an unpopular topic for discussion, but in recent decades they have received increased attention, due to both medical and economic factors. This review discusses the general concepts that characterize the negative consequences of surgical interventions in spinal neurosurgery: complications, adverse events, sentinel events, never events, collateral adverse outcomes. Classifications are given that allow systematizing these negative phenomena. Surgical treatment of the lumbar disk herniation is the most frequently performed spinal surgery. The true number of lumbar discectomies is difficult to estimate because this procedure is often not an isolated surgical intervention, but a step in a larger one. Being a routine surgical procedure, discectomy, performed in one or another way depending on the preferences of the surgeon and available equipment, is characterized by a rather low relative frequency of adverse events and complications compared to other types of spinal surgery. However, due to the significant number of interventions, the absolute figures may present a medical and economic problem. Most authors refer to the classic triad of “wrong level, wrong side, wrong patient” and foreign bodies in the area of surgical intervention as obvious medical errors. Damage to the intestine or peritoneum, trauma to the great vessels and trauma to the nerve roots are considered serious complications, but not always medical errors. The other most commonly reported adverse events of lumbar discectomy are durotomy, neurological complications, surgical wound complications, recurrent disc herniation, and reoperation. Until now, no clear classification of the negative consequences of lumbar discectomy, which would allow to verify the relationship between intraoperative adverse events (both surgical and anesthetic) and postoperative complications has been developed. In addition, it is extremely difficult, based on the criteria available in the literature, to identify a medical error in a number of iatrogenic complications, which requires further comprehensive study of the problem, since it has not only medical, but also legal consequences.