Case Reports / Journal of Clinical Neuroscience 21 (2014) 1049–1051


Rapidly progressive quadriparesis heralding disseminated coccidioidomycosis in an immunocompetent patient Lee A. Tan a, Manish K. Kasliwal a,⇑, Sukriti Nag b, John E. O’Toole a, Vincent C. Traynelis a a b

Department of Neurosurgery, Rush University Medical Center, Suite 855, 1653 W. Congress Parkway, Chicago, IL 60612, USA Department of Pathology, Rush University Medical Center, Chicago, IL, USA

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Article history: Received 14 July 2013 Accepted 19 July 2013

Keywords: Coccidioides Disseminated coccidioidomycosis Fungal infection Intramedullary Quadriparesis Spine

a b s t r a c t Coccidioides species are dimorphic fungi endemic to southwestern USA and northern Mexico. Disseminated coccidioidomycosis is rare with an estimated incidence of 1% in affected individuals and usually presents as meningitis when the central nervous system is involved. Spinal involvement with coccidioidomycosis, though not uncommon, predominantly manifests as osseous involvement leading to osteomyelitis and epidural abscess formation. Progressive quadriparesis as a presenting symptom secondary to intramedullary spinal cord coccidioidomycosis is very unusual and to our knowledge has not been described. We report a patient with disseminated coccidioidomycosis who presented with rapidly progressive quadriparesis due to cervical intramedullary spinal cord involvement. The absence of known coccidioidomycosis with atypical clinical presentation made the diagnosis elusive, requiring emergent cervical laminectomies with dural biopsy for decompression of the spinal cord and confirmation of the diagnosis. The patient eventually succumbed to the progressive course of the disease. Although rare, disseminated coccidioidomycosis can present as new, rapidly progressing quadriparesis in patients who have traveled to endemic areas. A high index of suspicion in such patients with appropriately directed laboratory investigations and consideration of early biopsy might unravel the diagnosis facilitating early antifungal treatment with the potential to minimize morbidity and mortality associated with disseminated coccidioidomycosis. Ó 2013 Elsevier Ltd. All rights reserved.

1. Introduction Coccidioides species are dimorphic fungi endemic to southwestern USA and northern Mexico, a region known as the lower Sonoran life zone. Inhalation of Coccidioides immitis or Coccidioides posadasii spores can cause a fungal infection known as coccidioidomycosis [1]. It has an estimated annual incidence of 150,000 in the USA [2]. About 60% of the infected individuals are asymptomatic [3]; symptomatic coccidioidomycosis usually manifests with pulmonary symptoms similar to community-acquired pneumonia [4]. Disseminated coccidioidomycosis is estimated to occur in 1% of all affected individuals, [3,4] with a higher incidence in immunocompromised patients, and usually presents as meningitis, cutaneous/soft-tissue nodules, and fungal osteomyelitis [5]. Progressive quadriparesis due to spinal cord involvement as the presenting symptom has not been described to our knowledge. We report a 55-year-old man who presented with rapidly progressive quadriparesis due to disseminated coccidioidomycosis with a review of the pertinent literature. 2. Case report A 55-year-old man presented with bilateral upper extremities weakness for several weeks. He was born in Mexico and moved to the USA at the age of 5. He had frequent visits to Mexico, with the last visit about 1 year before presentation. MRI of the spine showed leptomeningeal enhancement and extensive intramedullary T2-weighted signal change in the cervical spinal cord (Fig. 1). Cerebrospinal fluid (CSF) revealed elevated white cell count and proteins [white blood cells 355, 79% lymphocytes (normal range 0–10 per mm3), glucose 25 mg/dl (normal range 45–70 mg/dl) and protein of 3959 mg/dl (normal range 7–35 mg/ dl)]. A differential diagnosis of neurosarcoidosis, meningeal carcino⇑ Corresponding author. Tel.: +1 312 942 6644; fax: +1 312 942 2176. E-mail address: [email protected] (M.K. Kasliwal).

matosis secondary to hematological malignancy, and possible infection was entertained. His serum angiotensin converting enzyme level was not elevated; anti-nuclear antibody, rheumatoid factor, complement and antibody testing were also unremarkable with CSF negative for any bacterial growth and cryptococcal antigen. A chest CT scan performed for systemic work-up showed a small cavitary lesion in the right lung base. Concurrently, a bronchoscopy was done with a bronchoalveolar lavage (BAL) which grew Coccidioides immitis after 1 week. During the incubating period for the BAL culture, the patient was placed on high dose steroids to treat presumed sarcoidosis with some transient improvement of symptoms. The patient was even considered for emergent radiation treatment given his rapidly worsening symptoms for possible disseminated carcinomatosis, although cytology was negative for malignant cells. However, the patient rapidly progressed to quadriplegia with worsening mental status. In the absence of diagnosis, and rapidly progressive quadriparesis, neurosurgery was consulted and an emergent cervical laminectomy and decompression of the spinal cord with dural biopsy was performed. An external ventricular drain was also placed as the patient was comatose with development of hydrocephalus. While the BAL confirmed the presence of Coccidioides immitis, cultures from surgery and the meningeal biopsy also grew the same, establishing the diagnosis of disseminated coccidioidomycosis (Fig. 2). Once suspected, serum and CSF complement fixation (CF) tests were performed and showed a complement fixing antibody titer of 1:128 suggestive of disseminated coccidioidomycosis. MRI of the brain showed basal enhancement within multiple basal ganglia and cerebellar infarcts. The patient was placed on intravenous and intrathecal amphotericin B to treat disseminated coccidioidomycosis. Unfortunately the patient failed to improve neurologically and died 3 weeks after surgery. 3. Discussion Coccidioidomycosis is typically a mild disease that manifests with flu-like symptoms and a rash. However, in a small percentage


Case Reports / Journal of Clinical Neuroscience 21 (2014) 1049–1051

Fig. 1. Sagittal T1-weighted (left), post-contrast (center) and T2-weighted (right) MRI demonstrating minimal disc bulges with significant T2-weighted intramedullary hyperintensity and leptomeningeal enhancement.

Fig. 2. Dural surgical sample showing inflammation with collections of macrophages and neutrophils. Thick-walled spherules (arrowheads) which are consistent with that of Coccidioides immitis are present (hematoxylin and eosin stain, original magnification  20). The inset shows endospores (Gomori Silver-methenamine stain, original magnification  40). (This figure is available in colour at

of patients, it can become disseminated and may involve the central nervous system (CNS) and spine. Dissemination to the CNS can occur in up to 50% patients with disseminated coccidioidomycosis, even in immunocompetent individuals [6,7]. The most common presentation of CNS dissemination is basilar meningitis, which often causes hydrocephalus that requires CSF diversion. Most of the literature on spinal coccidioidomycosis has been focused on osseous involvement of the spine, which commonly presents with back pain, radiculopathy or myelopathy [8,9]. Non-osseous involvement of the spine has been rare and most commonly cited as nodular leptomeningeal enhancement [10,11]. Lammering et al. described a series of patients with concomitant brain and spinal involvement with coccidioidomycosis and reported the presence of intramedullary signal change in the spinal cord in 17–37% of patients along the course of the disease [12]. The authors attributed the T2-weighted signal change to vascular narrowing caused by inflammation in the presence of Coccidioides infection that eventually leads to insufficient arterial flow and venous congestion, which then in turn causes spinal cord edema and hypoxia [12,13]. Vascular involvement by the disease may account for the rapid progression of quadriparesis as seen in our patient, and high-

lights the importance of early recognition and treatment of this relentless infection. The consequence of unrecognized CNS coccidioidomycosis can be devastating, therefore early recognition and treatment of the disease is imperative to minimize mortality and morbidity associated with this condition [6]. Management of osseous spinal coccidioidomycosis is mainly medical, with surgery reserved for patients with significant neurological deficit due to compression or spinal instability, or intractable pain [9,14]. Azoles remain the treatment of choice and may need to be administered lifelong. Early diagnosis of CNS coccidioidomycosis requires a detailed patient history along with a combination of laboratory testing and imaging studies. Patients with a history of travel to endemic areas should raise the clinical suspicion for Coccidioides infection and should be evaluated with through work-up in spite of unusual radiological presentation. Serological testing with CF antibody titers in the CSF and blood may help diagnose the CNS involvement, although up to 12% of patients may have false negative results [15]. It is also possible for a patient to have concurrent non-disseminated coccidioidomycosis and a second separate CNS process, therefore CSF testing and tissue diagnosis are important for accurate diagnosis of disseminated CNS coccidioidomycosis, especially if the clinical condition deteriorates. However, CSF cultures and antibody tests are only positive in about half of these patients [5]. The CSF profile usually shows leukocytosis, decreased glucose level and increased protein level which is non-specific and can be seen in other diseases, including sarcoidosis and disseminated carcinomatosis [16,17]. Nevertheless, a CF test for immunoglobulin G (IgG) antibody against coccidioides may be helpful as the results are rapidly available compared to culture and may help initiate the treatment before irreversible injury. CSF cytology can be useful to rule out carcinomatosis in some cases, but the sensitivity of this test is reported be only 71% in one study [8]. Therefore, we believe that tissue diagnosis should be obtained promptly whenever possible if CNS coccidioidomycosis is suspected, especially if the presenting symptom is unusual and in the absence of any positive culture from extra-neural tissue or after a negative CF test from serum or CSF. In our patient, the initial clinical picture was confusing given the unusual presenting symptom of progressive quadriparesis. The spinal cord involvement seen on MRI mimicked imaging findings often seen in neurosarcoidosis and disseminated carcinomatosis. Steroid therapy was given for empiric treatment for presumed sarcoidosis due to the progressive neurological deficit and the CSF profile resembled that of sarcoidosis. The patient was even considered for empiric spinal cord irradiation given concern for carcino-

Case Reports / Journal of Clinical Neuroscience 21 (2014) 1051–1052

matosis. Although the patient was eventually taken for meningeal biopsy which ultimately confirmed the diagnosis of CNS coccidioidomycosis, there was a significant delay due to the extensive medical work-up. Therefore, CNS coccidioidomycosis should be high on the differential in any patient who presents with progressive neurological deficit and has been to an endemic area, in order to diagnose this relentless CNS infection which can be lethal or associated with severe morbidity if not timely recognized. Empirical therapy should be considered whilst awaiting culture results. 4. Conclusion Disseminated coccidioidomycosis can involve the spinal cord and mimic other inflammatory or neoplastic processes such as sarcoidosis and carcinomatosis. The clinical picture can be challenging if there is no prior diagnosis of coccidioidomycosis. Early recognition and confirmation of the diagnosis through a CF test for detection of IgG antibody, cultures from an extra-neural organ system if involved, or biopsy of the CNS lesions may be required to guide proper treatment and minimize the morbidity and mortality associated with this disease. Conflicts of Interest/Disclosures The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication.


[2] Borchers AT, Gershwin ME. The immune response in coccidioidomycosis. Autoimmun Rev 2010;10:94–102. [3] Smith CE, Beard RR. Varieties of coccidioidal infection in relation to the epidemiology and control of the diseases. Am J Public Health Nations Health 1946;36:1394–402. [4] Ampel NM. New perspectives on coccidioidomycosis. Proc Am Thorac Soc 2010;7:181–5. [5] Welsh O, Vera-Cabrera L, Rendon A, et al. Coccidioidomycosis. Clin Dermatol 2012;30:573–91. [6] Drake KW, Adam RD. Coccidioidal meningitis and brain abscesses: analysis of 71 cases at a referral center. Neurology 2009;73:1780–6. [7] Banuelos AF, Williams PL, Johnson RH, et al. Central nervous system abscesses due to Coccidioides species. Clin Infect Dis 1996;22:240–50. [8] Glantz MJ, Cole BF, Glantz LK, et al. Cerebrospinal fluid cytology in patients with cancer: minimizing false-negative results. Cancer 1998;82:733–9. [9] Kakarla UK, Kalani MY, Sharma GK, et al. Surgical management of coccidioidomycosis of the spine: clinical article. J Neurosurg Spine 2011;15: 441–6. [10] Erly WK, Bellon RJ, Seeger JF, et al. MR imaging of acute coccidioidal meningitis. AJNR Am J Neuroradiol 1999;20:509–14. [11] Wrobel CJ, Meyer S, Johnson RH, et al. MR findings in acute and chronic coccidioidomycosis meningitis. AJNR Am J Neuroradiol 1992;13:1241–5. [12] Lammering JC, Iv M, Gupta N, et al. Imaging spectrum of CNS coccidioidomycosis: prevalence and significance of concurrent brain and spinal disease. AJR Am J Roentgenol 2013;200:1334–46. [13] Feigin I, Budzilovich G, Weinberg S, et al. Degeneration of white matter in hypoxia, acidosis and edema. J Neuropathol Exp Neurol 1973;32:125–43. [14] Wrobel CJ, Chappell ET, Taylor W. Clinical presentation, radiological findings, and treatment results of coccidioidomycosis involving the spine: report on 23 cases. J Neurosurg 2001;95:33–9. [15] Szeyko LA, Taljanovic MS, Dzioba RB, et al. Vertebral coccidioidomycosis: presentation and multidisciplinary management. Am J Med 2012;125:304–14. [16] Clarke JL. Leptomeningeal metastasis from systemic cancer. Continuum (Minneap Minn) 2012;18:328–42. [17] Segal BM. Neurosarcoidosis: diagnostic approaches and therapeutic strategies. Curr Opin Neurol 2013;26:307–13.

References [1] Seitz AE, Prevots DR, Holland SM. Hospitalizations associated with disseminated coccidioidomycosis, Arizona and California, USA. Emerg Infect Dis 2012;18:1476–9.

Primary leptomeningeal melanoma Zhao-Yu Xie a, Kevin Li-Chun Hsieh a,⇑, Yuk-Ming Tsang a, Wing-Keung Cheung a, Chen-Hsi Hsieh b a b

Department of Radiology, Division of Medical Imaging, Far Eastern Memorial Hospital, Number 21, Section 2, Nanya S. Road, Banqiao District, New Taipei City 220, Taiwan Division of Radiation Oncology, Department of Radiology, Far-Eastern Memorial Hospital, New Taipei City, Taiwan

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Article history: Received 1 May 2013 Accepted 13 August 2013

Keywords: Brain tumor Central nervous system Primary leptomeningeal melanoma Seizure

a b s t r a c t Primary melanoma of the central nervous system is a rare melanocytic tumor typically located in the leptomeninges. We report a 57-year-old woman with an intracranial leptomeningeal melanoma who presented with myoclonic seizures. Brain CT scan and MRI revealed a hemorrhagic intracranial tumor. The tumor was completely removed and leptomeningeal melanoma was proven pathologically. Follow-up imaging studies up to 19 months showed no recurrence of the disease. Here we present radiological, gross, and pathological images of leptomeningeal melanoma, discuss its characteristics, and review the relevant literature. Ó 2013 Elsevier Ltd. All rights reserved.

1. Introduction

2. Case report

Melanocytic tumors of the central nervous system (CNS) are generally metastatic in origin. Primary melanocytic neoplasms are rare and normally derived from melanocytes in the leptomeninges. Here we report a rare case of a primary leptomeningeal melanoma, focusing on the radiological, gross, and pathological findings.

A 57-year-old woman visited our emergency department having suffered a seizure episode with loss of consciousness and rapid eyelid movement for more than 1 hour. The neurological examination revealed only mild weakness in the right extremities. No mucocutaneous or ocular pigmented lesions could be found on her skin upon physical examination. The plain brain CT scan (Fig. 1a) revealed a 3.2  3.4 cm hyperdense mass in the left superficial frontal lobe, with involvement of

⇑ Corresponding author. Tel.: +886 2 8966 7000. E-mail address: [email protected] (K.L.-C. Hsieh).

Rapidly progressive quadriparesis heralding disseminated coccidioidomycosis in an immunocompetent patient.

Coccidioides species are dimorphic fungi endemic to southwestern USA and northern Mexico. Disseminated coccidioidomycosis is rare with an estimated in...
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