Melissa W. Ko

A patient with encephalitis associated with NMDA receptor antibodies

Background A 34-year-old woman presented with headache, feverish sensation and anxiety, rapidly followed by homicidal ideation, aggressive agitation, seizures, hypoventilation, hyperthermia and prominent autonomic instability requiring intubation and sedation. She developed episodes of hypotension and bradycardia with periods of asystole lasting up to 15 seconds. Upon weaning off sedation, her eyes opened but she was unresponsive to stimuli. There was muscle rigidity, frequent facial grimacing, rhythmic abdominal contractions, kicking motions of the legs, and intermittent dystonic postures of the right arm.Investigations Routine laboratory testing, toxicology screening, studies for autoimmune and infectious etiologies, brain MRI scan, lumbar puncture, electroencephalogram, whole-body CT scan, abdominal ultrasound, paraneoplastic and voltage-gated potassium channel antibody serologies, analysis of N-methyl-D-aspartate receptor antibodies.Diagnosis Paraneoplastic encephalitis associated with immature teratoma of the ovary and N-methyl-D-aspartate receptor antibodies.Management Intensive care, mechanical ventilation, antiepileptics, laparotomy and left salpingo-oophorectomy, corticosteroids, plasma exchange, intravenous immunoglobulin, cyclophosphamide, physical therapy, and chemotherapy.

Neuro-ophthalmologic manifestations of paraneoplastic syndromes.

Paraneoplastic syndromes with neuro-ophthalmologic manifestations may involve the central nervous system, cranial nerves, neuromuscular junction, optic nerve, uvea, or retina. Most of these disorders are related to immunologic mechanisms presumably triggered by the neoplastic expression of neuronal proteins. Accurate recognition is essential to appropriate management.

Weight gain and recurrence in idiopathic intracranial hypertension A case-control study

Objective: To determine whether weight gain is associated with recurrence in idiopathic intracranial hypertension (IIH). Methods: Medical records of adult patients with IIH seen between 1993 and 2009 at 2 university hospitals were reviewed to identify those with and without recurrence. Patients with documented height and weight at presentation and at subsequent visits were studied. The Wilcoxon rank sum test was used to compare mean body mass index (BMI) and percent weight change between the groups of patients with recurrence and without recurrence. The signed-rank test was used for comparing BMI within groups at the various time points. Results: Fifty women with IIH were included in the analyses: 26 had IIH recurrence and 24 did not. Patients with recurrence had greater BMI at the time of recurrence compared to BMI at diagnosis (p = 0.02, signed-rank test). They also demonstrated a greater degree of weight gain between initial resolution and recurrence (BMI change +2.0 kg/m2 [−1.5 to 10.8]) compared to patients without recurrence (−0.75 kg/m2 [−35 to 3.6], p = 0.0009, Wilcoxon rank sum test). Patients without recurrence demonstrated stable weights (0%[95% CI −9.6 to 10.1%]), while patients with recurrence demonstrated a 6% weight gain ([−3.5 to 40.2%], p = 0.005), with an average rate of BMI gain of 1.3 kg/m2/year vs −0.96 kg/m2/year in those without recurrence. Conclusion: Patients with IIH recurrence had significant increases in BMI compared to patients without recurrence in this cohort. Patients with resolved IIH should be advised that weight gain may be a risk factor for IIH recurrence.

Idiopathic Intracranial Hypertension

Opinion statementIdiopathic intracranial hypertension (IIH) is a disorder of raised intracranial pressure of unknown etiology. For overweight or obese patients with IIH, weight reduction of 5% to 10% of total body weight at diagnosis is a long-term treatment strategy. Though not proven, the initiation of acetazolamide can assist in symptom reduction and resolution. In patients with either fulminant IIH or those on maximal medical management with progressive vision loss, intravenous steroids and acetazolamide can be initiated while surgical options are urgently arranged. Because of its lower complication rate, I prefer to use optic nerve sheath fenestration in settings of precipitous visual decline, but I have used cerebrospinal fluid diversion surgery in settings of vision loss with severe, intractable headache. Often, the choice of surgical intervention is individualized for the patient and the available expertise. In the future, results from the ongoing multicenter, double-blind, placebo-controlled Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) will provide important data regarding the efficacy of acetazolamide and the utility of diet and exercise.

Idiopathic intracranial hypertension and obesity.

Idiopathic intracranial hypertension (IIH), also known as primary pseudotumor cerebri syndrome (PTCS), is a condition of unknown etiology which affects primarily overweight, reproductive-aged women and causes increased intracranial pressure (ICP). This review discusses the recently revised diagnostic criteria for PTCS for adults and children. Additionally, the role of obesity in the epidemiology, etiology, and management of IIH as well as the current knowledge of obesity profiles and markers in IIH are reviewed. We also highlight the emerging, unifying theory of the neuroendocrine effects on the mineralocorticoid receptor to explain a possible mechanism for the increased cerebrospinal fluid production and ICP in secondary PTCS.

Supranuclear vertical gaze abnormalities in sporadic Creutzfeldt–Jakob disease

Supranuclear gaze palsies are an uncommon feature of Creutzfeldt-Jakob disease (CJD). Most reported cases of CJD with features of supranuclear gaze palsy are familial. We report 2 patients with supranuclear vertical gaze abnormalities associated with spongiform changes in the midbrain. Both patients were found to have sporadic CJD after genetic testing. Distinguishing familial from sporadic CJD in this setting has important genetic and epidemiological implications.

Primary diffuse leptomeningeal gliomatosis mimicking a chronic inflammatory meningitis.

Primary diffuse leptomeningeal gliomatosis (PDLG) is a rare, fatal, neoplastic condition of infiltrating glial cells into the meninges without evidence of primary tumor in the brain or spinal cord parenchyma. Primary diffuse leptomeningeal gliomatosis often presents with symptoms and physical findings of chronic inflammatory meningitis and raised intracranial pressure, and lacks specific clinical, radiologic, and diagnostic criteria. We report a case of PDLG diagnosed post-mortem, highlighting the diagnostic difficulty in identifying PDLG as the cause of chronic meningitis, even when a neoplastic etiology is suspected. Because multiple cytologies and even a leptomeningeal biopsy did not reveal the diagnosis ante-mortem, we emphasize the consideration of multi-site or repeat leptomeningeal biopsy when a persistent inflammatory infiltrate is found and neurological symptoms are progressive.

Acute promyelocytic leukemic involvement of the optic nerves following mitoxantrone treatment for multiple sclerosis

Mitoxantrone, the first immunosuppressant to receive FDA approval for treatment of worsening relapsing-remitting, secondary progressive, and progressive-relapsing multiple sclerosis (MS) is a DNA topoisomerase II inhibitor that has been associated with the development of acute promyelocytic myelogenous leukemia (APML). Central nervous system APML is a rare site of extramedullary involvement following mitoxantrone therapy. We report a patient with history of multiple sclerosis who developed bilateral optic nerve involvement as the primary manifestation of APML relapse following mitoxantrone treatment.

Visual improvement after optic nerve sheath decompression in a case of congenital hydrocephalus and persistent visual loss despite intracranial pressure correction via shunting.

Among the sequelae of persistent raised intracranial pressure (ICP) are ophthalmologic signs and symptoms, including cranial nerve palsies, visual field deficits, papilledema, and vision loss. Elevated pressure within the optic nerve sheath may not be relieved by shunt procedures, which can decrease generalized ICP. The authors present a case of acute visual loss in the setting of chronic hydrocephalus and multiple shunt revisions. Despite shunt correction resolving systemic symptoms of raised ICP, this child had persistent visual loss. Bilateral optic nerve sheath decompression was performed, and the visual acuity improved over the next 3 days. This case highlights the importance of routine ophthalmologic examination in patients with hydrocephalus and shunts and demonstrates the utility of optic nerve sheath decompression as a surgical intervention when shunting alone does not resolve visual loss.

Castleman disease presenting with pseudotumour cerebri and myasthenia gravis: A case report and literature review

ABSTRACT Castleman disease (CD) is a rare lymphoproliferative disorder that may present with various autoimmune, inflammatory, or neurologic syndromes. This is a case of a 21-year-old woman who presented with signs and symptoms of pseudotumour cerebri (PTC) who subsequently developed myasthenia gravis (MG), and was incidentally found to have a large mass in the posterior mediastinum. Upon resection, the mass was classified as unicentric CD involved with follicular dendritic cell sarcoma. Following treatment with IVIG in the setting of progressive weakness and dyspnea, she has had complete symptom resolution while maintained on a low dose of pyridostigmine for the last two years. There are 13 cases of MG and five cases of optic disc edema described as PTC associated with CD in the literature, but to our knowledge, this is the sole case reported of the intersection of all three conditions in one patient. Increased serum levels of interleukin-6 and vascular endothelial growth factor may provide clues as to the association of CD with these neurologic syndromes.