Bilateral Ptosis Research Articles

PSAT355 A Case Report Identifying Graves’ Ophthalmopathy in a Myasthenia Gravis Crisis and Response to Teprotumumab

Abstract Background Thyroid disease is relatively common in patients with Myasthenia Gravis (MG), affecting 5%–10% of patients, conversely, the prevalence of MG in patients with Graves’ disease is 0.14%. Of thyroid diseases seen in MG, Graves’ Disease (GD) is the most common. Graves ophthalmopathy (GO) is a known complication associated with GD, however, in patients with MG, its identification may be difficult, as both GD and MG may present with similar ocular signs and subtle differences. This case identifies GO in a MG crisis and its response to teprotumumab. Clinical Case A 53-year-old-woman with MG presented with one year of worsening bilateral eye and arm weakness, fatigue, eye pain, headaches and palpitations. Examination revealed bilateral ptosis, eyelid edema, and ⅘ bilateral upper extremity strength. Workup revealed suppressed TSH (<0.010, n 0.5-5.0 ml U/L) and elevated antibodies: Thyroid Stimulating Immunoglobulin (4.86, n <0.54 IU/L) and Thyrotropin Receptor Antibodies (TRAb) (8.08, n ≤1.75 IU/L). Thyroid ultrasound showed several bilateral cystic nodules and increased thyroid parenchyma vascularity without thyromegaly, suggestive of GD. Thyroid Uptake and Scan showed diffusely elevated 24-hour uptake (71%, n 10-30%) consistent with GD. Treatment was initiated with methimazole 5 mg daily. At follow up, she had symptoms of eyelid weakness, diplopia, headaches, and muscle weakness. Graves’ Ophthalmopathy Clinical Activity Score (CAS) was 5/10. Examination showed bilateral ptosis with eyelid edema, proptosis, conjunctival redness, and chemosis. Extraocular muscle movements intact without pain, normal pupils and visual fields. Ophthalmology review and orbital CT showed bilateral exophthalmos with extraocular muscle thickening consistent with thyroid eye disease (TED). The classic coke-bottle-sign of the anterior tendon of the inferior rectus muscles was noted. Given her presentation, clinical course and progression of TED, she commenced a teprotumumab treatment trial. Clinical improvement of GO was noted upon follow-up assessment after 5 doses of teprotumumab: CAS 2/10, decreasing proptosis on exam, and TRAb (3.86, n ≤1.75 IU/L). Conclusion This case highlights the potentially misleading clinical findings and difficult diagnoses of coexisting GO and MG. Although muscular weakness is common in GD, concomitant MG is rare and may cause profound additional morbidity. Ocular signs in both diseases may cause diagnostic confusion, although ptosis is more consistent with MG and lid retraction with GD alone. GO can mimic some of the neuromuscular and ophthalmologic signs of MG and can be easily missed or mistakenly attributed to either MG or GD. This may result in a delayed diagnosis/inappropriate treatment of GO, thus, clinicians should maintain suspicion for coexisting diagnoses. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Contribution of Stereotaxic Biopsy in the Management of Brain Tumors: About 101 Cases

Introduction: The advent of Stereotaxic Biopsy (STB) and the development of CT and MRI have improved the management of brain tumours. The aim of this study is to evaluate the role of STB in the management of brain tumors. Material and Methods: Retrospective study from 2000 to 2020 concerning 101 consecutive patients with brain tumours, having benefited from a STB, collected in the neurosurgery departments of the the public hospital establishment of AIT IDDIR and Mustapha and Mustapha BACHA university hospital center. The seat of the lesion is deep or functional (the Rolondic region, hemispherical, basal ganglia, lateral ventricles and brainstem and pineal region). STB was performed under CT guidance in all cases. For pineal tumours, arteriography with venographic time and preoperative MRI has been deemed useful to avoid hemorrhagic complications. Results: In 101 cases, the STB was conclusive on the first attempt (90%). The repetition of the STB made it possible to re-establish a precise diagnosis in (5.94%) It was malignant lesions (70% of the cases). The average age of the patients was 46 years (3 to 72) with a male predominance. The topography of the lesions is: 75.13% in the Rolondic region, Central Gray Nuclei, Brainstem and pineal region; 12.87% in the corpus callosum and lateral ventricles and 12.5% in the eloquent superficial lesion. Postoperative complications are dominated by mortality 5.9% followed by partial epileptic seizure 2.98% and severe neurological disorders 1.98%, bilateral ptosis 1.98% and hemiplegia 0.99%. Perioperative mortality fell from 10.45% before 2005 to 1% after 2006 (Chi-square; p = 0.010). Conclusion: STBs should be staged and repeated in case of inconclusive histology. For small deep lesions STB under MRI conditions is necessary. For pineal tumours, it must be performed by the transtemporal orthogonal approach.

Acute Onset Bilateral Ptosis in an Asymptomatic COVID Patient

Acute Onset Bilateral Ptosis in an Asymptomatic COVID Patient

235 EYES WIDE SHUT: A CASE OF BILATERAL PTOSIS FOLLOWING STROKE

Abstract Background Bilateral ptosis is a rare manifestation of midbrain stroke. It has been reported in case studies only, with no data on incidence rate, and no published case report in Ireland to date. Methods This is a retrospective case study of a man admitted to an acute stroke unit following collapse and unresponsiveness. A review of his medical records and radiological database was conducted. A PUBMED database search was conducted to search for similar cases. Results We present the case of a man who had a witnessed collapse whilst farming and was brought to hospital and presented with a Glasgow Coma Scale of 3. Imaging showed a normal CT Brain. MRI revealed 2cm acute bilateral thalamic and midbrain infarction. Following a brief period in ICU he was transferred to the acute stroke unit for multidisciplinary care. Despite improvements in his medical status and communication efforts, his inability to open his eyes contributed to a persistently low GCS. Neurological assessment revealed bilateral ptosis, fixed dilated pupils and oculomotor paralysis. These symptoms had a profound impact on his stroke recovery, impeding assessments and interventions and engagement in all realms (swallow and communication; mobility and function, cognitive-perceptual) whilst also limiting opportunities for social interaction. Once staff became aware of the ophthalmoplegia, strategies were implemented to optimise his participation and provide opportunities of recovery. Three months post stroke, he began to experience some return of unilateral eye-opening and bilateral horizontal movements (with diplopia) which greatly improved his overall performance. He was then transferred to the rehabilitation unit where he continues to progress. Conclusion Bilateral ptosis post stroke is rare and has a debilitating effect on participation in all aspects of living and interaction with the environment. This presentation has previously been described as “reverse locked-in-syndrome” which accurately represents its impact.

P.79 Late onset oculopharyngeal muscular dystrophy in a POLG1-related progressive external ophthalmoplegia (PEO), a diagnostic challenge

POLG1, a nuclear gene, encodes the catalytic subunit of mitochondrial DNA polymerase γ involved in mtDNA maintenance. Autosomal dominant or recessive inherited phenotypes related to POLG1 mutations display clinical variability, including isolated or syndromic progressive external ophthalmoplegia (PEO). Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset autosomal dominant myopathy characterized by progressive ptosis, dysphagia, and limb weakness. In OPMD patients, the 5’ (GCN)10 repeat region of the PABPN1 gene is abnormally expanded up to 17 repeats. The (GCN)11 enlarged repeat allele is described as a polymorphism or a recessive allele. However, rare cases of patients with a single (GCN)11 heterozygous allele are known to express a late-onset OPMD phenotype. Reporting a patient associating POLG1 compound heterozygous mutations and a PABPN1 (GCN)11 heterozygous expansion with mixed phenotype, we aim to point out the potential clinical overlap and diagnostic challenge linked to these entities. A 74-year-old male patient presented with progressive bilateral ptosis and mild dysphagia at the age of 70. CK and lactate levels were normal. Electrodiagnostic tests demonstrated a mild sensory neuropathy and muscle biopsy showed atrophic and necrotic fibers, increased internal nuclei and twelve COX-negative fibers. Electron microscopy identified electrodense deposits in mitochondria but no intranuclear inclusions. Muscle oxidative phosphorylation analyses demonstrated complexes I and II diminished activities. POLG1 sequencing revealed the previously described c.1760C>T, p.(Pro587Leu) pathogenic variant and the c.233T>A, p.(Met78Lys) novel variant. Segregation study allowed to conclude a trans conformation in the proband. We report a patient presenting with progressive ptosis associated with two potential coexisting etiologies ascertained by polemic evidence. On one hand, biallelic variants were found on his POLG1 gene, associated with features of mitochondrial defects on muscle biopsy. On the other hand, the phenotype also fits with OPMD and is associated with a PABPN1 (GCN)11 heterozygous expansion allele. This peculiar observation illustrates the potential diagnostic challenge that may represent a progressive ptosis, especially in elderly patients. POLG1, a nuclear gene, encodes the catalytic subunit of mitochondrial DNA polymerase γ involved in mtDNA maintenance. Autosomal dominant or recessive inherited phenotypes related to POLG1 mutations display clinical variability, including isolated or syndromic progressive external ophthalmoplegia (PEO). Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset autosomal dominant myopathy characterized by progressive ptosis, dysphagia, and limb weakness. In OPMD patients, the 5’ (GCN)10 repeat region of the PABPN1 gene is abnormally expanded up to 17 repeats. The (GCN)11 enlarged repeat allele is described as a polymorphism or a recessive allele. However, rare cases of patients with a single (GCN)11 heterozygous allele are known to express a late-onset OPMD phenotype. Reporting a patient associating POLG1 compound heterozygous mutations and a PABPN1 (GCN)11 heterozygous expansion with mixed phenotype, we aim to point out the potential clinical overlap and diagnostic challenge linked to these entities. A 74-year-old male patient presented with progressive bilateral ptosis and mild dysphagia at the age of 70. CK and lactate levels were normal. Electrodiagnostic tests demonstrated a mild sensory neuropathy and muscle biopsy showed atrophic and necrotic fibers, increased internal nuclei and twelve COX-negative fibers. Electron microscopy identified electrodense deposits in mitochondria but no intranuclear inclusions. Muscle oxidative phosphorylation analyses demonstrated complexes I and II diminished activities. POLG1 sequencing revealed the previously described c.1760C>T, p.(Pro587Leu) pathogenic variant and the c.233T>A, p.(Met78Lys) novel variant. Segregation study allowed to conclude a trans conformation in the proband. We report a patient presenting with progressive ptosis associated with two potential coexisting etiologies ascertained by polemic evidence. On one hand, biallelic variants were found on his POLG1 gene, associated with features of mitochondrial defects on muscle biopsy. On the other hand, the phenotype also fits with OPMD and is associated with a PABPN1 (GCN)11 heterozygous expansion allele. This peculiar observation illustrates the potential diagnostic challenge that may represent a progressive ptosis, especially in elderly patients.

MYASTHENIA GRAVIS PRECIPITATED BY ASYMPTOMATIC COVID-19 INFECTION, VACCINE, OR BOTH? HOW GENETIC PREDISPOSITION AND IMMUNE RESPONSES PLAY A ROLE IN THE NEUROMUSCULAR JUNCTION

MYASTHENIA GRAVIS PRECIPITATED BY ASYMPTOMATIC COVID-19 INFECTION, VACCINE, OR BOTH? HOW GENETIC PREDISPOSITION AND IMMUNE RESPONSES PLAY A ROLE IN THE NEUROMUSCULAR JUNCTION

Weber syndrome – clinical-imaging correlations

An 89 years-old female patient was brought in by the family for altered mental status and left-sided motor deficit. Medical history revealed high blood pressure for which the patient was receiving anti-hypertensive treatment. Upon examination, the patient presented altered mental status, dysarthria, dysphagia, left central facial palsy, ataxic tetraparesis with marked paralysis on the left side, bilateral Babinski signs, right-sided ophthalmoplegia with limitation of gaze in all directions, left-sided skew deviation, limited abduction and upgaze movements of the left eye, and bilateral ptosis (complete on the right side and incomplete on the left side). The clinical picture was thus compatible with a vertebrobasilar stroke. A possible diagnosis of Weber syndrome was suggested, given the left-sided hemiparesis and right-sided ophthalmoplegia. Both head CT and brain MRI confirmed this by demonstrating a right-sided thalamo-mesencephalic subacute ischemic stroke. No cardio-embolic source was identified on cardiac assessment. Consequently, the patient was discharged with antiplatelet therapy, statin and anti-hypertensive treatment. We provide a short review on Weber syndrome, emphasizing the correlations between the clinical pictures and imaging findings.

Phenotype, genotype, and management of congenital fibrosis of extraocular muscles type 1 in 16 Chinese families

PurposeCongenital fibrosis of extraocular muscles type 1 (CFEOM1), a classical subtype of CFEOM, is characterized by restrictive ophthalmoplegia and ptosis. It is mainly caused by aberrant neural innervation of the extraocular muscles. This study aimed to investigate the genetic characteristics and clinical manifestations of CFEOM1 in Chinese families.MethodsThe clinical data, including ocular examinations, magnetic resonance imaging (MRI), and surgical procedures of affected individuals from 16 Chinese CFEOM1 families, were collected. The genomic DNA of 16 probands and their family members were sequenced for causative KIF21A gene mutations. Linkage analysis using microsatellite markers across KIF21A was also conducted.ResultsAffected individuals were presented with bilateral non-progressive ptosis, restricted horizontal eye movement, fixed infraduction of both eyes, compensatory chin-up head position, and neuromuscular abnormalities. Three heterozygous KIF21A mutations, c.2860C > T (p.R954W) (in eight families), c.2861G > T (p.R954L) (in two families), and c.2861G > A (p.R954Q) (in two families) were identified, which implied that hotspot mutations were common in Chinese CFEOM1 families. Germline Mosaicism was likely to be the cause of affected individuals with asymptomatic parents without KIF21A mutations presented in the eight families. Two affected individuals underwent modified levator muscle complex suspension surgery and achieved a good result without any complications.ConclusionInstead of evaluating the whole CFEOM1 gene variant, hotspot mutations could be given priority for screening. The occurrence of germline mosaicism has to be taken into account in genetic counseling. Patients with CFEOM1 who have ptosis may benefit from an innovative surgical procedure called modified levator muscle complex suspension.

The effectiveness of additional medical management of patients in the early stages after reconstructive interventions on the auxiliary apparatus of the eye: assessment of changes in the tissues of the ocular surface and eyelids

Purpose: to evaluate the effectiveness and safety of combination therapy using the moisturizing ophthalmic solution, Hyloparin-Comod®, and the lubricating ophthalmic agent Parin-Pos® in complex medical management in the early stages after reconstructive interventions on the auxiliary apparatus of the eye.Material and methods. The clinical group consisted of 30 patients (40 eyes) aged 18 to 75 (m = 58.46 ± 7.31), of which 7 (23.3 %) were men; and 23 (74.7 %) women. Of these, 18 patients had ptosis of the upper eyelid (of which 10 had bilateral ptosis), 8 had inversion of the eyelids and 4 had eversion. All patients underwent reconstructive plastic surgery on the auxiliary apparatus of the eye: ptosis of the upper eyelid was treated by various methods depending on its type: 18 patients received plastic surgery of the levator aponeurosis (in 8 cases on both eyes; simultaneously, blepharochalasis resection was performed), 4 patients underwent levator shortening, 4 patients underwent eyebrow suspension (of these, 2 patients had the procedure on both eyes, hanging to the eyebrow – 4 operations (both eyes were operated on in two patients), 2 had tarzomyectomy; 8 had elimination of inversion, and 4 had elimination of eversion. In the postoperative period, instillations of antiseptics and antibiotics were supplemented by tear replacement and keratoprotective therapy: Hyloparin-Comod® was instilled 3 times during the day, while Parin-Pos® ointment was placed under and on the eyelids before going to bed. The course of treatment lasted 1 month. All patients underwent a standard ophthalmological examination before surgery as well as 2 weeks, 1 month and 3 months after surgery. The criteria for evaluating the effectiveness of treatment were the condition of the eyelid skin on a pointwise scale (Manchester scar scale), the result of biomicroscopy / biomicroscopy with fluorescein staining of the conjunctiva and cornea, Norn test.Results. In all cases of the use of Hyloparin-Comod® and Parin-Pos® combination, good subjective tolerability was noted, the patients had no complaints of discomfort due to the use of drops or ointment.Conclusion. The results obtained demonstrate that the proposed combination of drugs contributes to improving the favorable condition of eyelid skin and wound healing with the formation of a delicate scar, rapid resolution of conjunctival and eyelid swelling, prevention of corneal microerosions, minimization of corneal epithelial edema and tear film stability.

Effect of external eyelid weighting on eyelid and eyebrow position in normal and ptosis patients.

This study aims to characterize the physiologic response of both eyelid and eyebrow position to increasing downward forces simulated by external weights. In this prospective observational study, both normal individuals and patients affected by ptosis were tested. External eyelid weights were placed on one upper eyelid with incrementally increasing weight from 0.2 to 2.4g. The eyelid carrying the weight was randomly selected for normal subjects and patients with bilateral ptosis, whereas for unilateral ptosis, the ptotic eyelid was utilized. Photographs were obtained at baseline and with increasing weight until MRD1 reached 0 on the weighted side or, until 2.4g was reached. Eyelid and brow position on the weighted and unweighted sides were digitally measured in millimeter. Primary outcome measures were change in the margin to reflex distance (MRD1) and pupil to brow distance (PTB) with weight on the weighted and unweighted sides for normal and ptosis subjects. The weighted eyelid MRD1 decreased linearly with increasing weight. This was true for normal and ptosis subjects. The unweighted eyelid MRD1 increased linearly with increasing weight. This was also the case for both normal and ptosis subjects. With increasing weight, PTB increased linearly on the weighted side. No significant intergroup differences were noted. In normal and ptosis subjects, when external weight on the eyelid is incrementally increased, the weighted eyelid MRD1 decreases, the unweighted eyelid MRD1 increases, and both brows elevate in a linear fashion.

Bilateral ptosis caused by patent foramen ovale-associated stroke.

Bilateral ptosis caused by patent foramen ovale-associated stroke.

Novel copy number variation of COLQ gene in a Moroccan patient with congenital myasthenic syndrome: a case report and review of the literature

BackgroundCongenital myasthenic syndromes (CMSs) are rare genetic diseases due to abnormalities of the neuromuscular junction leading to permanent or transient muscle fatigability and weakness. To date, 32 genes were found to be involved in CMSs with autosomal dominant and/or recessive inheritance patterns. CMS with acetylcholinesterase deficiency, in particular, was determined to be due to biallelic mutations of COLQ gene with early-onset clinical signs. Here, we report clinical features and novel molecular findings of COLQ-related CMS in a Moroccan patient with a review of the literature for this rare form.Case presentationIn this study, we report the case of a 28-month-old Moroccan female patient with hypotonia, associated to axial muscle weakness, global motor delay, bilateral ptosis, unilateral partial visual field deficiency with normal ocular motility, and fatigable muscle weakness. Clinical exome sequencing revealed a novel homozygous deletion of exon 13 in COLQ gene, NM_005677.4(COLQ):c.(814+1_815-1)_(954+1_955-1) del p.(Gly272Aspfs*11). This finding was subsequently confirmed by quantitative real-time PCR (qPCR) in the proband and her parents. In silico analysis of protein-protein interaction network by STRING tool revealed that 12 proteins are highly associated to COLQ with an elevated confidence score. Treatment with Salbutamol resulted in clear benefits and recovery.ConclusionsThis clinical observation illustrates the important place of next-generation sequencing in the precise molecular diagnosis of heterogeneous forms of CMS, the appropriate management and targeted treatment, and genetic counseling of families, with a better characterization of the mutational profile of this rare disease in the Moroccan population.

EXAMINATION TECHNIQUE OF PATIENT WITH NON HODGKINS LYMPHOMA AND LEPTOMENINGEAL METASTASIS

Lepomeningeal metastasis - one of the neurological complications for a number of malignant tumors, is occurs as a result of infiltration of leptomeninges and subarachnoid space by malignant cells. A 68-year-old male patient with Non Hodgkins lymphoma, came to our clinic with complaints of bilateral drooping of the eyelids, more expressed on the left; nausea, vomiting, severe headaches, dizziness, weakness in the limbs. During the examination, the patient's consciousness was clear, questions were answered adequately. The signs of damage to the third pair of cranial nerves - the oculomotor nerve: bilateral ptosis and mydriasis were revealed in the patient. Thus, the patient was recommended intrathecal treatment (IT) and was referred to an oncologist.

494 Epidermolysis bullosa pruriginosa, muscular dystrophy, and immune-mediated myasthenia gravis in a patient with homozygous nonsense PLEC mutation

A 26-year-old female presented with epidermolysis bullosa prurogompsa (EBP) since infancy, hair loss, proximal motor weakness, nasal tone speech, swallowing problem, and droopy eyes at age 20. Upon neurological examination, normal cognition, inability to walk unassisted, bilateral ptosis with full range of extraocular movements, weak gag reflex, generalized muscle atrophy, and decreased deep tendon reflexes were detected. Her electromyography revealed small polyphasic muscle unit action potentials, minimal insertional activities, myopathic changes, motor and sensory increased latency, decreased amplitude, reduced velocity, and normal F wave.

TWNK in Parkinson's Disease: A Movement Disorder and Mitochondrial Disease Center Perspective Study.

BackgroundParkinsonian features have been described in patients harboring variants in nuclear genes encoding for proteins involved in mitochondrial DNA maintenance, such as TWNK.ObjectivesThe aim was to screen for TWNK variants in an Italian cohort of Parkinson's disease (PD) patients and to assess the occurrence of parkinsonism in patients presenting with TWNK‐related autosomal dominant progressive external ophthalmoplegia (TWNK‐adPEO).MethodsGenomic DNA of 263 consecutively collected PD patients who underwent diagnostic genetic testing was analyzed with a targeted custom gene panel including TWNK, as well as genes causative of monogenic PD. Genetic and clinical data of 18 TWNK‐adPEO patients with parkinsonism were retrospectively analyzed.ResultsSix of 263 PD patients (2%), presenting either with isolated PD (n = 4) or in combination with bilateral ptosis (n = 2), carried TWNK likely pathogenic variants. Among 18 TWNK‐adPEO patients, 5 (28%) had parkinsonism.ConclusionsWe show candidate TWNK variants occurring in PD without PEO. This finding will require further confirmatory studies. © 2022 Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

Ophthalmoparesis and Bilateral Ptosis as a Rare Manifestation of Todd's Phenomenon: Case Report and Review

Todd's paresis or phenomenon (TP) is a focal weakness in a part of the body after a seizure. Seizure is an abrupt change in behavior caused by the cerebral cortex's electrical hyper-synchronization of neuronal networks. After the seizure, there is usually a transition period from the ictal state to the pre-seizure baseline level of awareness and function, referred to as the postictal period. Postictal symptoms include many systems, including sensory, motor, and psychosis. This phenomenon is named after Robert Bentley Todd, who first described it. Todd's paresis can be confused with other conditions, most commonly a stroke. Postictal ocular manifestation may be accompanied by aphasia or hemiplegia, but isolated gaze palsy is rarely reported. We are reporting a rare and first known isolated ophthalmoparesis and ptosis as postictal findings with no structural abnormalities present in imaging studies and complete resolution over three weeks on its own as an atypical postictal phenomenon. Patients with an underlying structural abnormality of the brain are more susceptible to Todd's phenomenon. Unusual manifestations of Todd's phenomenon are rare but clinically relevant and are decisive in therapeutic decision-making. Our patient presents a rare manifestation of Todd's phenomenon as ptosis and ophthalmoparesis in an elderly male with no underlying structural brain abnormalities that resolved within three weeks. Further research into the causes is needed to distinguish it from a stroke

225 A rare case of recurrent unsteadiness due to Miller Fisher syndrome

A 71-year-old male presented to the emergency department with unsteadiness, blurred vision, slurred speech and sensory changes. He had progressive loss of reflexes. After initial horizontal nystagmus he developed bilateral ophthalmoplegia with bilateral ptosis and impaired coordination with an ataxic gait. This was preceded by productive cough and loose stools.The patient was diagnosed with Miller Fisher Syndrome (MFS), with a positive anti-GQ1b antibody and CSF albuminocytologic dissociation supporting the diagnosis. This was the patient’s second episode of MFS. The first had occurred twenty-seven years earlier with a similar presentation and examination findings.This poster then reviews the clinical presentation, management and recurrence of Miller Fisher Syndrome. gavriella.levinson@nhs.net

Pembrolizumab-induced Myasthenia Gravis: Literature Review of Ocular Manifestations and a Refractory Case.

Immune checkpoint inhibition is a new and promising therapy approved for the treatment of various malignancies. Pembrolizumab is a potent tumor suppressor that acts by upregulating the immune system to recognize cancer cells which may result in disrupted self-tolerance. We describe a case and perform a literature review of myasthenia gravis with ocular manifestations after treatment with pembrolizumab. Our case had bilateral ptosis refractory to conventional treatment, and she remained functionally blind as a result. The literature review included 28 cases of immune-related myasthenia gravis, and a 30% mortality rate excluding deaths from primary cancer progression was shown. Under half had full symptom resolution (n=13, 46%), and there was no clear correlation between specific management strategies and prognosis. Patients with isolated ocular myasthenia gravis (n=9, 32%) were twice as likely to be symptom-free after treatment compared with generalized myasthenia gravis (75% vs. 39%). Respiratory involvement was associated with twice the mortality rate (60% vs. 33%) and triple the risk of noncomplete symptom resolution (20% vs. 61%). The majority of cases had their pembrolizumab discontinued (n=20, 71%), but 3 were successfully rechallenged by utilizing prophylactic low-dose steroids. Patients with immune-related myasthenia gravis experience increased mortality and morbidity but if steroid-responsive, may benefit from the reintroduction of anti-programmed cell death protein 1 therapy for end-stage malignancy with close monitoring. A high index of clinical suspicion for immune-related adverse effects are critical in an era of rising immunotherapy use.

The coincidence of Guillain‐Barré syndrome and myasthenia gravis

Background The occurrence of both Guillain-Barré syndrome (GBS) and Myasthenia Gravis (MG) conditions in the same individual is rare. The underlying pathophysiology was assumed to be an autoimmune humoral mechanism. A molecular mimicry in which a cross-reaction between autoantibodies and myelin sheath of peripheral nerves and acetylcholine receptors of the neuromuscular junction (NMJ) cannot be excluded as an underlying cause. Case presentation An 18-year-old female patient was examined. She was presented with symptoms of generalized weakness and distal weakness in both upper and lower extremities, more pronounced on the right side and with associated right foot drop and bilateral ptosis. The electrophysiological study was performed and the AChR antibody titre was determined. The patient was diagnosed with GBS and MG. Conclusions In conclusion, GBS and MG are two different neurological entities with different pathophysiology. New onset or persistence of symptoms in a patient with GBS treated with IVIG or plasmapheresis should probe for another autoimmune neurological illness, preferably autoimmune neuromuscular disorders like MG.

Abstract #1165370: Unique Case of an Adult Patient with Neurofibromatosis Type 1 with Noonan Syndrome (NFNS) Features and Idiopathic Hypoparathyroidism Complicated by Recurrent Episodes of Hypo- and Hypercalcemia

NFNS is a rare RASopathy consisting of phenotypic features of neurofibromatosis type I (NF-1) and Noonan syndrome (NS) features. Endocrine disorders in this syndrome can commonly involve growth hormone related disorders. Here, we present the management of an adult patient with a unique case of NFNS with idiopathic hypoparathyroidism. A 22-year-old male with NFNS diagnosed in early childhood presented to our facility. NF1-like features included multiple café-au-lait spots, Lisch nodules, and basal ganglia hamartomas. NS-like features included webbed neck, bilateral ptosis, low posteriorly set ears, short stature, and intellectual delay. Patient’s family history was significant for NF-1 in a brother and father, and a maternal grandmother with hypocalcemia throughout her childhood. Genetic testing was significant for a positive NF-1 gene panel and a negative NS gene panel, consistent with NFNS. It should be noted that at age 15, he presented with pre-B acute lymphoid lymphoma (ALL) and hypocalcemia. At the time, his ionized calcium level (iCa) was 0.57 mg/dL (n = 4.5-5.6 mg/dL) and total calcium was 4.2 mg/dL (n = 8.8-10.3 mg/dL). He had hyperphosphatemia of 9.2 mg/dL (n = 3.0-4.5 mg/dL) with a low PTH of 3.7 pg/mL (n = 10-65pg/mL) and hypomagnesemia of 1.4 mg/dL (n = 1.7-2.2 mg/dL). The patient was treated with calcitriol, calcium carbonate, vitamin D and magnesium gluconate. Since his hypoparathyroidism diagnosis, the patient has multiple readmissions for recurrent episodes of hypocalcemia and hypercalcemia. During his first hypercalcemic episode, the patient also had acute pancreatitis associated with a chemotherapy agent. He required treatment with aggressive fluids, subcutaneous calcitonin, furosemide, and termination of home calcium and calcitriol supplementation. Following these initial episodes, the patient has continued to have recurrent episodes of hypocalcemia and hypercalcemia that were not associated with any other etiology such as acute pancreatitis, chronic immobilization, or chemotherapy regimens. While there have been a few previous reports of hypoparathyroidism in NS [1, 2], none were noted in association with NFNS. In our extensive literature review, we have not been able to find another case report of idiopathic hypoparathyroidism in NFNS. We feel that the uniqueness of the case coupled with the challenges associated with the adulthood management of recurrent hypercalcemia and hypocalcemia in this patient makes this a very interesting case to present.