A case of Rhizopus infection in an immunocompetent IVDA host

Introduction: Mucormycosis is a rare fungal infection most commonly seen in patients with neutropenia, diabetic ketoacidosis, or prolonged use of corticosteroids. Here we present an unusual case of isolated cerebral mucormycosis in a young, immunocompetent patient. Case: A 36 year-old female with chronic Hepatitis C and intravenous drug abuse (IVDA) presented with sudden hemiparesis of the left upper and lower extremities. Her Glasgow Coma Scale was 15. MRI brain revealed a gadolinium-enhancing lesion adjacent to the right basal ganglia and thalamus consistent with an abscess, with surrounding vasogenic edema, mass effect causing right-to-left midline shift involving her right lateral ventricle (Figures 1 and 2). The abscess was surgically debrided and biopsy of the lesion revealed multinucleated giant cells and scattered groupings of branching fungal forms consistent with Rhizopus oryzae infection. Her remaining infectious and immunologic workup was unremarkable, including undetectable Hepatitis C RNA and absent HIV antibodies. During her hospital course, she exhibited new neurological findings including right lateral gaze palsy, left facial weakness, left hemi-neglect, and left ankle clonus. This was attributed to worsening vasogenic edema despite a medical regimen including IV amphotericin B and anidulafungin. Subsequently, isavuconazole was added. She continued on this regimen for four weeks after her initial debridement and was discharged to an in-patient rehabilitation center. On follow up examinations, she has exhibited gradual improvement in her strength, however she continues to have visual field deficits and requires assistance with activities of daily living. Discussion: Mucormycosis is a rare, life-threatening fungal infection predominantly affecting immunocompromised hosts. The most significant risk factors for this infection include diabetic ketoacidosis, neutropenia, prolonged high-dose glucocorticoid therapy, bone marrow or solid organ transplantation, iron overload, and IVDA. Clinical presentation often reflects underlying risk factors for disease. For example, diabetic patients are likely to present with sinus involvement whereas patients with transplanted organs and malignancy more commonly present with pulmonary infection. Disseminated disease is most commonly seen in patients in an iron-overloaded state or those treated with deferoxamine. Isolated cerebral infection constitutes just 5% of all mucormyosis infections, but has a fatality rate exceeding 60%. Despite its rarity, however, isolated cerebral mucormycosis is the most common presentation among IVDA, constituting 62% of mucormycosis infections in this subgroup. Brain lesions are most commonly located within the basal ganglia, likely secondary to hematogenous seeding of the perforating branches of the Middle Cerebral Artery. It has been hypothesized that illicit injection drugs contaminated with mucormyosis spores enter the systemic arterial circulation before seeding the brain. Improved survival rates are seen among those patients treated with early stereotactic biopsy and aggressive amphotericin B therapy. Conclusion: For patients with a history of IVDA who present with brain abscess (especially in the basal ganglia), mucormycosis should be on the clinicians’ differential diagnosis. Early intervention with stereotactic brain biopsy and amphotericin B, as well as abscess debridement, can dramatically increase the likelihood of survival and can minimize permanent neurologic sequelae.https://scholarlycommons.henryford.com/merf2020caserpt/1076/thumbnail.jp

Foix Alajouanine Syndrome Mimicking Longitudinally Extensive Transverse Myelitis

Objective: To describe an interesting case of Foix-Alajouanine Syndrome presenting as a longitudinally extensive transverse myelitis (LETM). Background: Foix-Alajouanine Syndrome is caused by a spinal dural arteriovenous malformation and presents as paraparesis and progressive walking impairment. It most commonly involves the thoracolumbar region and affects elderly men. Though treatable, it is a cause of progressive myelopathy often misdiagnosed or missed. Case Discussion: A 77-year-old man with a history of coronary artery disease presented with a one-year history of progressive lower extremity paresthesia, weakness, gait instability, and recurrent falls. He had no lumbar or lower extremity pain. He had no bladder incontinence. His symptoms were attributed to lumbar spinal stenosis and he underwent L3-L4 lumbar decompression at an outside hospital with no improvement. MRI of the lumbar spine without contrast done at the outside facility was reviewed and it showed an LETM from T8 through the tip of the conus medullaris. MRI of the entire spine was repeated with gadolinium. MRI lumbar spine with gadolinium showed flow voids at the dorsal aspect of T8-T9 consistent with a Type I spinal dural AV fistula. This was confirmed by the spinal angiogram. The patient had a negative MRI brain and cervical spine imaging. The spinal fluid analysis was unremarkable. Aquaporin-4 antibody and anti-MOG antibody tests were negative. He underwent a laminectomy with microsurgical obliteration of the AV fistula and regained 50% of his lower extremity strength within 48 hours of his surgery and continues to improve with physical therapy. Conclusion: Foix-Alajouanine Syndrome should be considered in the differential diagnosis of LETM. It is a reversible cause of progressive myelopathy and needs a careful review of imaging, laboratory data, and clinical findings.https://scholarlycommons.henryford.com/merf2020caserpt/1106/thumbnail.jp

Altered high-energy phosphate and membrane metabolism in Pelizaeus-Merzbacher disease using phosphorus magnetic resonance spectroscopy

Pelizaeus-Merzbacher disease is an X-linked recessive leucodystrophy of the central nervous system caused by mutations affecting the major myelin protein, proteolipid protein 1. The extent of the altered in vivo neurochemistry of protein, proteolipid protein 1 duplications, the most common form of Pelizaeus-Merzbacher disease, is, however, poorly understood. Phosphorus magnetic resonance spectroscopy is the only in vivo technique that can assess the biochemistry associated with high-energy phosphate and membrane phospholipid metabolism across different cortical, subcortical and white matter areas. In this cross-sectional study, whole-brain, multi-voxel phosphorus magnetic resonance spectroscopy was acquired at 3 T on 14 patients with Pelizaeus-Merzbacher disease with protein, proteolipid protein 1 duplications and 23 healthy controls (all males). Anabolic and catabolic levels of membrane phospholipids (phosphocholine and phosphoethanolamine, and glycerophosphoethanolamine and glycerophosphocholine, respectively), as well as phosphocreatine, inorganic orthophosphate and adenosine triphosphate levels relative to the total phosphorus magnetic resonance spectroscopy signal from 12 different cortical and subcortical areas were compared between the two groups. Independent of brain area, phosphocholine, glycerophosphoethanolamine and inorganic orthophosphate levels were significantly lower (P = 0.0025, P \u3c 0.0001 and P = 0.0002) and phosphocreatine levels were significantly higher (P \u3c 0.0001) in Pelizaeus-Merzbacher disease patients compared with controls. Additionally, there was a significant group-by-brain area interaction for phosphocreatine with post-hoc analyses demonstrating significantly higher phosphocreatine levels in patients with Pelizaeus-Merzbacher disease compared with controls across multiple brain areas (anterior and posterior white matter, superior parietal lobe, posterior cingulate cortex, hippocampus, occipital cortex, striatum and thalamus; all P ≤ 0.0042). Phosphoethanolamine, glycerophosphoethanolamine and adenosine triphosphate levels were not significantly different between groups. For the first-time, widespread alterations in phosphorus magnetic resonance spectroscopy metabolite levels of Pelizaeus-Merzbacher disease patients are being reported. Specifically, increased high-energy phosphate storage levels of phosphocreatine concomitant with decreased inorganic orthophosphate across multiple areas suggest a widespread reduction in the high-energy phosphate utilization in Pelizaeus-Merzbacher disease, and the membrane phospholipid metabolite deficits suggest a widespread degradation in the neuropil content/maintenance of patients with Pelizaeus-Merzbacher disease which includes axons, dendrites and astrocytes within cortex and the myelin microstructure and oligodendrocytes within white matter. These results provide greater insight into the neuropathology of Pelizaeus-Merzbacher disease both in terms of energy expenditure and membrane phospholipid metabolites. Future longitudinal studies are warranted to investigate the utility of phosphorus magnetic resonance spectroscopy as surrogate biomarkers in monitoring treatment intervention for Pelizaeus-Merzbacher disease

COVID-19 in multiple sclerosis patients and risk factors for severe infection

Multiple sclerosis (MS) patients have been considered a higher-risk population for COVID-19 due to the high prevalence of disability and disease-modifying therapy use; however, there is little data identifying clinical characteristics of MS associated with worse COVID-19 outcomes. Therefore, we conducted a multicenter prospective cohort study looking at the outcomes of 40 MS patients with confirmed COVID-19. Severity of COVID-19 infection was based on hospital course, where a mild course was defined as the patient not requiring hospital admission, moderate severity was defined as the patient requiring hospital admission to the general floor, and most severe was defined as requiring intensive care unit admission and/or death. 19/40(47.5%) had mild courses, 15/40(37.5%) had moderate courses, and 6/40(15%) had severe courses. Patients with moderate and severe courses were significantly older than those with a mild course (57[50-63] years old and 66[58.8-69.5] years old vs 48[40-51.5] years old, P = 0.0121, P = 0.0373). There was differing prevalence of progressive MS phenotype in those with more severe courses (severe:2/6[33.3%]primary-progressing and 0/6[0%]secondary-progressing, moderate:1/14[7.14%] and 5/14[35.7%] vs mild:0/19[0%] and 1/19[5.26%], P = 0.0075, 1 unknown). Significant disability was found in 1/19(5.26%) mild course-patients, but was in 9/15(60%, P = 0.00435) of moderate course-patients and 2/6(33.3%, P = 0.200) of severe course-patients. Disease-modifying therapy prevalence did not differ among courses (mild:17/19[89.5%], moderate:12/15[80%] and severe:3/6[50%], P = 0.123). MS patients with more severe COVID-19 courses tended to be older, were more likely to suffer from progressive phenotype, and had a higher degree of disability. However, disease-modifying therapy use was not different among courses

Foix-Alajouanine Syndrome Mimicking Longitudinally Extensive Transverse Myelitis

Foix-Alajouanine syndrome is an arteriovenous malformation causing subacute congestive myelopathy that can lead to progressive paraplegia. It typically affects the lower thoracic and lumbosacral levels. Arteriovenous fistula (AVF) leads to increased venous pressure, decreasing the arteriovenous pressure gradient and leading to a decrease in spinal cord perfusion, oedema and necrosis. Early recognition and surgical intervention can result in a good prognosis

Foix-Alajouanine Syndrome Mimicking Longitudinally Extensive Transverse Myelitis

Objective: To describe an interesting case of Foix-Alajouanine Syndrome presenting as a longitudinally extensive transverse myelitis (LETM). Background: Foix-Alajouanine Syndrome is caused by a spinal dural arteriovenous malformation and presents as paraparesis and progressive walking impairment. It most commonly involves the thoracolumbar region and affects elderly men. Though treatable, it is a cause of progressive myelopathy often misdiagnosed or missed. Case Discussion: A 77-year-old man with a history of coronary artery disease presented with a one-year history of progressive lower extremity paresthesia, weakness, gait instability, and recurrent falls. He had no lumbar or lower extremity pain. He had no bladder incontinence. His symptoms were attributed to lumbar spinal stenosis and he underwent L3–L4 lumbar decompression at an outside hospital with no improvement. MRI of the lumbar spine without contrast done at the outside facility was reviewed and it showed an LETM from T8 through the tip of the conus medullaris. MRI of the entire spine was repeated with gadolinium. MRI lumbar spine with gadolinium showed flow voids at the dorsal aspect of T8–T9 consistent with a Type I spinal dural AV fistula. This was confirmed by the spinal angiogram. The patient had a negative MRI brain and cervical spine imaging. The spinal fluid analysis was unremarkable. Aquaporin-4 antibody and anti-MOG antibody tests were negative. He underwent a laminectomy with microsurgical obliteration of the AV fistula and regained 50% of his lower extremity strength within 48 hours of his surgery and continues to improve with physical therapy. Results: N/A Conclusions: Foix-Alajouanine Syndrome should be considered in the differential diagnosis of LETM. It is a reversible cause of progressive myelopathy and needs a careful review of imaging, laboratory data, and clinical findings

Floating heads: An Occi-dental discovery of bálint syndrome

Objective: To report a case of transient Bálint Syndrome in the setting of diaschisis. Background: Bálint syndrome is the cortical visual syndrome consisting of simultagnosia, oculomotor apraxia, and optic ataxia that occurs due to damage of bilateral parieto-occipital lobes. We present a unique case of Bálint syndrome in a patient with bilateral ischemic stroke of the occipital lobes only. Design/Methods: N/A Results: A 51 year old left-handed male with relevant history of hypertension, diabetes mellitus, coronary artery disease and prior right-sided embolic stroke presents for acute generalized weakness and progressively worsening vision to the point when he could no longer feed himself or get out of the car. Upon arrival, the patient stated, “I see a lot of floating heads in the room”. He was not able to comprehend that the room was filled with people. On further examination, his visual acuity was only mildly diminished. The patient was hesitant to grasp objects with his eyes open, missing by inches each time but had no difficulty grasping objects with his eyes closed. He could not track objects with his eyes and resorted to moving his head horizontally across the room. MRI brain showed bilateral occipital infarcts, acute on the left, and acute/subacute on the right. He was admitted to the stroke unit for further workup. After 24 hours, the patient\u27s oculomotor apraxia resolved and his simultagnosia improved, however his optic ataxia persised. Conclusions: Our patient presented with Bálint syndrome after developing bilateral occipital stroke. His parietal lobes were unaffected. This case highlights the concept of focal diaschisis. It is much more common for subcortical deficits to present this way. Very rarely do corticallyrelated clinical deficits present as a result of focal diaschisis, yet here is a patient with symptoms associated with lesions from an entirely different cortical lobe

Clinical spectrum of stiff person syndrome associated with glutamic acid decarboxylase antibodies

Objective: The aim of this study was to examine the clinical characteristics and associated diagnosis of the SPS. Background: Stiff person syndrome (SPS) is an immune-mediated neurological disorder that can cause rigidity of the axial and limb muscles. About 80% of patient with SPS have had high-titer antibodies against glutamic acid decarboxylase (GAD), and 15% have antibodies to glycine receptors. Design/Methods: Retrospective chart review of patients with SPS and positive GAD antibody who were seen over 5 years was performed. Demographics, detailed clinical information, and diagnostic data were recorded. Coexisting autoimmune diseases and serologies were reviewed. Results: Nine patients were included in this study, 7 women and 2 men. The median age at symptom onset was 47 years. Six patients had positive Gad antibody and 3 were negative. Primary diagnosis was stiff person syndrome (n=4), cerebellar ataxia (n=2), PERM (n=2) and sensory neuropathy/neuronopathy (n=1). Commonly associated antibodies were islet cell antibody and neuronal voltage-gated potassium channel. Type 1 diabetes, seizures, and thyroid disease were commonly associated with the diagnosis. Three patients had an EMG finding suggestive of SPS and two of these patients had negative GAD antibody. Conclusions: Women are commonly affected by the disease. There is a phenotypic variation of the disease as previously reported in the literature. EMG is helpful in the diagnosis of negative GAD antibody patients where clinical suspicion for SPS is high