Bilateral External Ophthalmoplegia Research Articles

Miller–Fisher syndrome – A diagnostic conundrum – A case report and review of literature

Miller–Fisher syndrome is a rare subvariant of Guillian–Barre syndrome, presenting with ophthalmoplegia, ataxia, and areflexia. We present a 37-year-old male with progressive bilateral external ophthalmoplegia with moderate left-eye ptosis. He developed myalgia, ataxia, and absent deep tendon reflexes. He was initially treated with thiamine infusion and pyridostigmine because of possible Wernicke’s encephalopathy or myasthenia with no improvement. Lumbar puncture revealed acellular smear with high protein. He was switched to IV immunoglobulin therapy proceeding which he showed improvement. We present this case due to its unusual nature and complex diagnostic conundrum.

Bickerstaff encephalitis in childhood: a review of 74 cases in the literature from 1951 to today.

Bickerstaff brainstem encephalitis (BBE) is a rare autoimmune disease characterized by the subacute onset of bilateral external ophthalmoplegia, ataxia, and decreased level of consciousness. BBE is part of a group of rare autoimmune diseases in children that can affect the nervous system at any level. The onset of neurological deficits is often sudden and nonspecific. The diagnosis is based on clinical findings and abnormal findings on cerebrospinal fluid (CSF), electroencephalography (EEG), electromyography (EMG), and magnetic resonance imaging (MRI). BBE is associated with the presence of the antiganglioside antibody, anti-GQ1b and anti-GM1. Intravenous immunoglobulin (IVIg) and plasma exchange are often used as treatments for these patients. We conducted a review on clinical presentation, diagnosis, treatment and outcome of reported cases of BBE. 74 cases are reported in the literature from the first cases described in 1951 to today. The prevalence is unknown while the incidence is higher in males. In 50% of cases, BBE occurs following respiratory or gastrointestinal tract infections. The most frequent initial symptoms were consciousness disturbance, headache, vomiting, diplopia, gait disturbance, dysarthria and fever. During illness course, almost all the patients developed consciousness disturbance, external ophthalmoplegia, and ataxia. Lumbar puncture showed pleocytosis or cytoalbuminological dissociation. Abnormal EEG and MRI studies revealed abnormalities in most cases. Anti-GQ1b antibodies were detected in more than half of the patients; anti-GM1 antibodies were detected in almost 40% of patients. Treatment guidelines are missing. In our analysis, steroids and IVIg were administered alone or in combination; as last option, plasmapheresis was used. BBE has a good prognosis and recovery in childhood is faster than in adulthood; 70% of patients reported no sequelae in our analysis. Future studies need to investigate pathogenesis and possible triggers, and therapeutic possibilities.

Kearns–Sayre Syndrome with Bilateral Ptosis and External Ophthalmoplegia: A Rare Case Report

Abstract
 Introduction : Kearns-Sayre syndrome (KSS) is a rare genetic disorder caused by a deletion of mitochondrial DNA (mtDNA) segment, typically characterized by a triad of symptoms includes external ophthalmoplegia, pigmentary retinopathy and appeared before the age of 20. The prevalence rate is about 1–3 per 100.000 individuals. It was diagnosed based on clinical features and supported by biochemical, radiological, histologic, and molecular genetic tests.
 Case Illustration : 26-year-old male with bilateral ptosis, chronic progressive external ophthalmoplegia, pigmentary retinopathy was shown from ophthalmology examination and associated with hearing loss. Physical examination showed short stature, wasting, and weakness of limb muscles. MRI examination revealed focal brain atrophy on bilateral parietal regions.
 Discussion : Mitochondrial DNA defect led to dysfunction of the central nervous system, endocrine system, extraocular muscle, myocardium, skeletal muscle, and other multiple systems. The clinical findings in this patient are appropriate for classical signs and symptoms of KSS. Central nervous involvementis shown by the neuroimaging result. There is no cardiac involvement suggested by normal cardiology examination. Although muscle pathology and molecular genetic analysis can play a great role to diagnose KSS, the classical triad of clinical signs plus one of the other symptoms could establish KSS diagnosis.
 Conclusion : KSS is a rare genetic disorder and challenging to diagnose. However, if a patient presents with the classic triad of symptoms, clinicians should have a high level of suspicion for the disorder. Additionally, It is important to perform a thorough evaluation to rule out other conditions that can cause similar symptoms.

Pediatric Miller Fisher Syndrome and Ocular Myasthenia Gravis (A Reminder of Clinical Mimicry): A Case Report

AbstractMiller Fisher syndrome (MFS) is a rare immune-mediated neuropathy that often presents with diplopia and bilateral external ophthalmoplegia. Other neurological deficits may occur such as ataxia and areflexia but not in all cases. Although MFS is a clinical diagnosis, serological confirmation is possible by identifying the anti-GQ1b antibody found in the majority of patients. Myasthenia gravis is an autoimmune disorder of the availability of acetylcholine receptors in the neuromuscular junction. Ocular myasthenia gravis is a disease subtype characterized by variable patterns of weakness of extraocular muscles, eyelid elevator, and orbicular muscle in which the initial sign in most adults and children is ptosis. We report a child with MFS who presented with clinical signs suggestive of ocular myasthenia gravis, but in whom the correct diagnosis was made on the basis of serological testing for the anti-GQ1b antibody. We aim to highlight the similarity between the two rare conditions and address the importance of early liaison with neurologists and ophthalmologists in reaching to the proper diagnosis.

Bilateral external ophthalmoplegia due to uremia in Goodpasture syndrome

Several ophthalmic manifestations have been reported in patients with uremia due to chronic kidney disease (CKD). These include chronic sore eyes, ischemic optic neuropathy, and retinal detachment. In this case report, we discuss a patient of Goodpasture syndrome undergoing hemodialysis for CKD who presented with a complaint of diplopia. The patient had bilateral near-total external ophthalmoplegia, which initially progressed and remained constant at the last follow-up. The patient was neurologically stable with normal neuroimaging; however, his serum creatinine and blood urea levels remained persistently elevated despite regular hemodialysis. After considering several differential diagnoses, we finally arrived at a diagnosis of bilateral external ophthalmoplegia secondary to uremia and propose potential mechanisms for its pathogenesis.

A Rare Case of Botulism in an Adult Patient

Presentation of botulism in adults is extremely rare and symptoms can be easily confused for symptoms of acute stroke, Guillain-Barre, or myasthenia gravis. The purpose of this clinical case report is to ensure adult botulism will be included in the differential diagnoses for a patient with this presentation so swift and accurate care can be provided to ensure optimal patient outcome. A 41-year-old-female presented with complaints of sudden onset of difficulty speaking. The patient reports a history of intravenous polysubstance abuse and symptoms progressed to bilateral facial weakness, ptosis, and external ophthalmoplegia. With no notable findings from a non-contrast computed tomography and magnetic resonance imaging and given the symptoms, a diagnosis of wound botulism from intravenous drug use was made. Botulism antitoxin was given and the patient was admitted into the intensive care unit for supportive follow-up care. A colony of Clostridium species was discovered in this patient’s arm and the patient showed significant improvement after a few days of care.

Enhancement of cranial nerves, conus medullaris, and nerve roots in POLG mitochondrial disease.

A 20-year-old female patient was admitted to our department due to ptosis, double vision, and difficulty walking. The symptoms had evolved during the course of 2 months. She had never been very athletic and was described as always having been a “slow runner,” but otherwise her previous history was unremarkable. There was no family history of neurologic disease. There were no preceding triggering factors such as infections, fever, or physical stress, and the patient did not take valproate. On examination, she had bilateral external ophthalmoplegia and ptosis, grade 4 proximal and distal paresis in the lower extremities, grade 4 distal paresis in the upper extremities, distal sensory loss (for all sensory modalities), and sensory ataxia. After several months, she started experiencing a very slow improvement, which is—at the present moment—still incomplete.

CONGENITAL MYOPATHIES (CNM): P.148Centronuclear myopathy with BIN1-like myopathology and DNM2 mutation

A limited number of genetically proven cases of BIN1-CNM have been described. DNM2-CNM is more frequent and the main biopsy characteristics is fibers with radiating sarcomeric strands along with nuclear centralization. To present a Brazilian case of DNM2 mutation and muscle biopsy with main features compatible with BIN1-CNM histopathology. Case report. A 58-year-old woman was born as a ``weak child'' with the ``eyes closed''. She had reduced spontaneous movements, delayed motor milestones and a motor limitation in follow other children in motor activities. Although motor weakness she was able to graduate in the university. Additional and more recent complains were hypersomnia and cognitive impairment. Consultation revealed: bilateral symmetrical ptosis and external ophthalmoplegia; motor deficit predominant at pelvic than scapular gilder; symmetric atrophy and weakness in distal lower limb. MFM scale had total score of 65.62% (D1=35.89%; D2=86.11%; D3=85.71%) and FVC was 32%. Recent Montreal cognitive assessment (MoCA) was 22/30. Cerebrospinal fluid showed protein of 82 mg/dL and Pandy positive. Biceps brachii biopsy showed several fibers with nuclear clustering centrally located and myofibers with one central nucleus. Type 1 fiber atrophy, type 2 hypertrophy and few fibers with radiating sarcomeric strands were also seen, thus predicting a CNM with BIN1 mutation. Surprisingly muscle MRI was compatible with DNM2-CNM and a cerebral MRI disclosed meningioma. A panel of new generation sequencing for myopathies showed a pathogenic variant in Ch19:10.904.508C>T (c.1105C>T) diagnosing a DNM2-CNM related. After a successful neurosurgery, the patient never acquired spontaneous ventilation, as was suggestive by MFM and FVC, remained in intensive care unit for four months, had multiples episodes of septicemia and died. Our case expands histopathological phenotypes of DNM2-CNM and reinforce the features of pelvis and legs MRI in DNM2 mutation.

One-sided triangle: A case of double vision

A 51-year-old woman presented with acute diplopia and was found to have ptosis and complete bilateral external and internal ophthalmoplegia. She had normal reflexes and gait. Serological testing showed elevated levels of GQ1b ganglioside autoantibodies, making the diagnosis of Miller Fisher syndrome. This case illustrates an atypical presentation of the Miller Fisher variant of Guillain-Barre syndrome, which should be considered in all patients presenting with bilateral ophthalmoplegia.

Intracranial hypotension mimicking chronic progressive external ophthalmoplegia

ABSTRACTIntracranial hypotension (ICH) is characterized by low cerebrospinal fluid pressure, postural headaches, and diffuse pachymeningeal enhancement on magnetic resonance imaging (MRI). A variety of ophthalmoparetic manifestations have been reported in the context of the ICH. The authors describe an unusual case of a 64-year-old woman who presented with rapid onset of headaches, bilateral upper-lid ptosis, and blurring of vision within 4 days after sustaining a trivial head injury. She was noted to have bilateral symmetrical ophthalmoplegia and ptosis-simulating chronic progressive external ophthalmoplegia. MRI revealed characteristic features of ICH. Subsequent autologous epidural patch therapy led to resolution of the headache and imaging findings; however, her ptosis and motility disorder persisted. Despite existing therapeutic measures for ICH, irreversible cranial nerve damage may ensue due to significant cerebral decent or ischemic injury.

Case of congenital fibrosis of the extraocular muscles type 1 with progressive cerebellar ataxia

AbstractA 70‐year‐old women presented classical CEFOM1 phenotypes such as bilateral ptosis and external ophthalmoplegia, but also progressive cerebellar ataxia, carrying a previously reported heterozygous missense mutation of KIF21A p.Arg941Gln. The present case is the first report of CFEOM1 showing cerebellar atrophy with hypoperfusion, mainly of the vermis, indicating that cerebellar function should be carefully evaluated in CFFOM1 patients.

両側外眼筋麻痺の眼球運動評価における定量的測定の有用性

両側外眼筋麻痺の眼球運動評価における定量的測定の有用性

Clinical profile and outcome of cerebral venous sinus thrombosis at tertiary care center

ABSTRACT Background: Thrombosis of the cerebral venous sinuses (CVST) is an uncommon form of stroke, usually affecting young individuals. Clinical features of CVST are diverse, and for this reason, high degree of clinical suspect is mandatory to diagnose the conditions. Materials and Methods: This study was conducted over a period of 1 year (Jan 2011 to Dec 2011). This was a retrospective, observational, and noninterventional study. This study was conducted in the Department of Medicine at a tertiary care teaching center. Total 50 patients where diagnosis of CVST was confirmed by computed tomography/magnetic resonance imaging brain venogram were included in this study. All patients with diagnosis of CVST were treated according to the standard protocol and guidelines. Statistical Analysis: The mean and standard deviation were obtained. The Chi-square test was used to analyze the data and P < 0.05 was considered as statistically significant. Results: Of total 50 patients with diagnosis of CVST, 21 (42%) were males and 29 (58%) were females with 39 ± 10 years and 29 ± 7 years, respectively. Total 45 (90%) patients presented with symptoms of headache and vomiting, 13 (26%) had seizures, 12 (24%) had hemiplegia, and 19 (38%) had fever. A total of 13 (26%) patients had papilledema on fundoscopy. Total 9 (31%) out of 29 patients had diagnosis of CVST during peripartum period. Total 12 (24%) patients had hyperhomocysteinemia. Total 23 (46%) patients had sagittal sinus thrombosis, 10 (20%) had multiple sinus thrombosis, 16 (32%) had sigmoid/transverse sinus thrombosis. There was 1 (2%) patient who had bilateral cavernous sinus thrombosis, who presented with bilateral proptosis, conjunctival congestion, and external ophthalmoplegia with a history of acute or chronic maxillary and sphenoid sinusitis. Total 38 patients had evidence of infection in the form of fever, paranasal sinus (PNS) infections, Chronic suppurative otitis media (CSOM). Total 19 (38%) patients had a history and evidence of dehydration. Total 8 (16%) patients died during the course of treatment and 42 (84%) were discharged with partial and/or total recovery. Three (6%) patients required neurosurgical intervention in the form of decompressive craniotomy. Eight (16%) patients died with cerebral edema with transtentorial herniation. The mean age of death in male was significantly greater than in female patients with P < 0.02. Majority of patients succumbed had sigmoid, transverse, and/or multiple sinus involvement. Patients with multiple sinus thrombosis had greater case fatality rate. Conclusions: The current study highlights the burden of CVST in the study population with headache and vomiting, which was the most common presenting complaint. The superior sagittal sinus thrombosis was the most common and bilateral cavernous sinus thrombosis was the uncommon affection in CVST. One third of female population was affected in peripartum period. The infection and/or dehydration was the most commonly associated precipitating event for development of CVST and more than one fifth of the population had evidence of hyperhomocysteinemia. Mortality was more in patients with affection of sigmoid, transverse, and/or multiple sinus involvement in male patients and superior sagittal sinus thrombosis in female patients. The treatment of CVST has to be aggressive as morbidity and mortality is relatively minimal compared with the arterial stroke.

Effectiveness of Pyridoxine and Pyridostigmine in the Treatment of Vincristine-Induced Bilateral Ptosis and External Ophthalmoplegia: A Case Report

Osman Okan Olcaysu*, Ahmet Altun**, Elif Olcaysu***, Sertac Argun Kivanc**, Zuhal Keskin Yildirim**** *Erzurum Region Education and Research Hospital, Clinic of Ophthalmology, Erzurum, Turkey **Fatih Sultan Mehmet Education and Research Hospital, Clinic of Ophthalmology, Istanbul, Turkey ***Uludag University Faculty of Medicine, Department of Ophthalmology, Bursa Turkey ****Ataturk University Faculty of Medicine, Department of Pediatrics, Erzurum, Turkey

Kearns-Sayre syndrome

Kearns-Sayre syndrome (KSS) is a rare neuromuscular disorder. We report a case of a 14-year-old boy diagnosed and treated as myasthenia gravis for (4) years who was eventually diagnosed with KSS. He reported to us 3 years after initial presentation of mild drooping of eyelids with increased severity of ptosis, bilateral external ophthalmoplegia, and atypical retinitis pigmentosa. On multispecialty consultation, he was found to have right bundle branch block, wasting and weakness of limb muscles, and hearing loss. Sartorius muscle biopsy revealed ragged red fibres on trichrome stain. All these findings confirmed the diagnosis of Kearns-Sayre Syndrome (KSS). The take home message is to have a high index of suspicion for KSS when encountering cases of musculoskeletal disorders in subjects below 20 years of age in view of high morbidity and mortality associated with this syndrome.

Clinical profile and outcome of cerebral venous sinus thrombosis at tertiary care center.

Background:Thrombosis of the cerebral venous sinuses (CVST) is an uncommon form of stroke, usually affecting young individuals. Clinical features of CVST are diverse, and for this reason, high degree of clinical suspect is mandatory to diagnose the conditions.Materials and Methods:This study was conducted over a period of 1 year (Jan 2011 to Dec 2011). This was a retrospective, observational, and noninterventional study. This study was conducted in the Department of Medicine at a tertiary care teaching center. Total 50 patients where diagnosis of CVST was confirmed by computed tomography/magnetic resonance imaging brain venogram were included in this study. All patients with diagnosis of CVST were treated according to the standard protocol and guidelines.Statistical Analysis:The mean and standard deviation were obtained. The Chi-square test was used to analyze the data and P < 0.05 was considered as statistically significant.Results:Of total 50 patients with diagnosis of CVST, 21 (42%) were males and 29 (58%) were females with 39 ± 10 years and 29 ± 7 years, respectively. Total 45 (90%) patients presented with symptoms of headache and vomiting, 13 (26%) had seizures, 12 (24%) had hemiplegia, and 19 (38%) had fever. A total of 13 (26%) patients had papilledema on fundoscopy. Total 9 (31%) out of 29 patients had diagnosis of CVST during peripartum period. Total 12 (24%) patients had hyperhomocysteinemia. Total 23 (46%) patients had sagittal sinus thrombosis, 10 (20%) had multiple sinus thrombosis, 16 (32%) had sigmoid/transverse sinus thrombosis. There was 1 (2%) patient who had bilateral cavernous sinus thrombosis, who presented with bilateral proptosis, conjunctival congestion, and external ophthalmoplegia with a history of acute or chronic maxillary and sphenoid sinusitis. Total 38 patients had evidence of infection in the form of fever, paranasal sinus (PNS) infections, Chronic suppurative otitis media (CSOM). Total 19 (38%) patients had a history and evidence of dehydration. Total 8 (16%) patients died during the course of treatment and 42 (84%) were discharged with partial and/or total recovery. Three (6%) patients required neurosurgical intervention in the form of decompressive craniotomy. Eight (16%) patients died with cerebral edema with transtentorial herniation. The mean age of death in male was significantly greater than in female patients with P < 0.02. Majority of patients succumbed had sigmoid, transverse, and/or multiple sinus involvement. Patients with multiple sinus thrombosis had greater case fatality rate.Conclusions:The current study highlights the burden of CVST in the study population with headache and vomiting, which was the most common presenting complaint. The superior sagittal sinus thrombosis was the most common and bilateral cavernous sinus thrombosis was the uncommon affection in CVST. One third of female population was affected in peripartum period. The infection and/or dehydration was the most commonly associated precipitating event for development of CVST and more than one fifth of the population had evidence of hyperhomocysteinemia. Mortality was more in patients with affection of sigmoid, transverse, and/or multiple sinus involvement in male patients and superior sagittal sinus thrombosis in female patients. The treatment of CVST has to be aggressive as morbidity and mortality is relatively minimal compared with the arterial stroke.

Genetic diseases affecting the eyelids

The molecular basis of a number of inherited diseases that affect the eyelids has been elucidated over the last two decades. Due to the vast number of these diseases, a clinician may become overwhelmed by the volume of data, making it difficult to incorporate newer information into his or her clinical practice. This article intends to review the recent developments of inherited diseases that affect the eyelids that a typical oculoplastic surgeon will encounter. This review proposes categorizing genetic diseases affecting the eyelids on rarity and whether the disease manifests itself at birth or later in life. Based on this classification system the following 10 diseases (the first five manifesting at birth, the last five later in life) are considered more likely to be encountered by the typical oculoplastic surgeon and reviewed in detail: blepharophimosis-ptosis-epicanthus inversus syndrome, congenital fibrosis of the extraocular muscles, lymphedema-distichiasis syndrome, neurofibromatosis type 1, congenital myasthenic syndrome, oculopharyngeal muscular dystrophy, chronic progressive external ophthalmoplegia, myotonic dystrophy, neurofibromatosis type 2, and basal cell nevus syndrome. The remaining known genetic disorders that affect the eyelids are considered less likely to be encountered by the typical oculoplastic surgeon and are listed in tabular form. It is prudent for the oculoplastic surgeon to be knowledgeable of inherited disorders that affect the eyelids to aid in accurate diagnosis, counseling, and treatment. The development of future therapies may at some point make treatment of these diseases no longer surgical. http://links.lww.com/COOP/A4.

An 85-year-old woman with Miller Fisher syndrome

Miller Fisher's syndrome (MFS) commonly presents in the fourth and fifth decades and are rare in people over 70 years. An 85-year-old female with no significant medical history presented with upper extremity anesthesia, ptosis, and unsteady gait. The patient had a history of hypertension and diabetes mellitus. Physical examination showed bilateral total external ophthalmoplegia, areflexia, and cerebellar ataxia. Radiological and laboratory studies were unremarkable. Lumbar puncture showed albuminocytological dissociation. The combined history, physical examination, and lumbar puncture results established a presumptive diagnosis of MFS. Intravenous immunoglobulin was given for 5 days. The patient gradually improved 10 days after the onset of symptoms. Ophthalmoplegia had fully recovered after 6 months. To the best of our knowledge, this case represented the oldest patient with MFS.

Biotin-Responsive Ophthalmoplegia / Dystonia

A 10-year-old girl with a 4-month history of abnormal gait and dysarthria had bilateral external ophthalmoplegia, dystonia, and altered mental status.

Bilateral External Ophthalmoplegia in Biotin-Responsive Basal Ganglia Disease

A 10-year-old girl with a 4-month history of abnormal gait and dysarthria was admitted to the hospital with altered mental status that had progressed over the previous 3 days in the context of febrile illness. The patient's family reported that she did not use drugs, and the family history is remarkable only for consanguinity. On physical examination, she was confused, having generalized dystonia and bilateral external ophthalmoplegia, and she was anarthric. The results of toxicologic and autoimmune, cerebrospinal fluid, thyroid, bacterial and viral, and metabolic studies, including tandem mass spectrometry, urine for organic acids, and levels of lactic acid, ammonia, acylcarnitines, copper, ceruloplasmin, biotin, and thiamine, were all negative. An initial magnetic resonance imaging (MRI) of the brain showed abnormal signal intensity alterations bilaterally involving the cerebellum, basal ganglia, medial nucleus of the thalamus with a characteristic “bat-wing” appearance, and cerebral cortex (Figure). The affected areas showed increased signal consistent with vasogenic edema on diffusion-weighted images and apparent diffusion coefficient map (not shown). The MRI findings suggested biotin-responsive basal ganglia disease. Sequencing of the SLC19A3 gene identified a pathogenic homozygous mutation c.1264A>G (p.Thr422Ala). The patient was administered thiamine and biotin, achieving marked improvement in her confusion, extraocular movements, and ambulation during the next 4 days. Three months later, she exhibited only mild dysarthria. Repeated brain MRI showed resolution of the vasogenic edema with residual atrophy and gliosis in the basal ganglia (Figure). The physical exam finding of acute to subacute, bilateral external ophthalmoplegia is telling for an energy breakdown, as occurs with biotin-responsive basal ganglia disease, thiamine deficiency, and mitochondrial defects. That exam finding would lead one to examine the midbrain, thalamus, and basal ganglia on brain MRI. Biotin-responsive basal ganglia disease is an autosomal recessive, underdiagnosed pan-ethnic treatable condition, related to thiamine transporter-2 deficiency. It needs to be included in the differential diagnosis for unexplained acute dystonia, bilateral external ophthalmoplegia and encephalopathy, and neuroimaging showing vasogenic edema in the bilateral putamen and caudate nuclei, infratentorial and supratentorial cortex, and brainstem, because a therapeutic trial with thiamine and biotin can be lifesaving.1Ozand P.T. Gascon G.G. Al Essa M. Joshi S. Al Jishi E. Bakheet S. et al.Biotin-responsive basal ganglia disease: a novel entity.Brain. 1998; 121: 1267-1279Crossref PubMed Scopus (136) Google Scholar, 2Serrano M. Rebollo M. Depienne C. Rastetter A. Fernández-Álvarez E. Muchart J. et al.Reversible generalized dystonia and encephalopathy from thiamine transporter 2 deficiency.Mov Disord. 2012; 27: 1295-1298Crossref PubMed Scopus (35) Google Scholar