The patient is a 52-year-old right-handed male with a medical history of vitiligo, obstructive sleep apnea and polymyalgia rheumatica (PMR) for which he was maintained on chronic oral prednisone. Approximately 3 weeks prior to presentation at our institution, he had an insidious onset of a pulsating bitemporal, bioccipital positional headache which worsened when he assumed a supine position. This progressed to include nausea, intermittent diplopia, phonophobia and gait instability. The patient's wife also noted a significant decrement in his short-term memory and executive functions.
He presented to his local emergency department. An MRI with and without IV contrast showed left basilar leptomeningeal enhancement prompting a lumbar puncture. Cerebrospinal fluid (CSF) analysis revealed elevated protein, hypoglycorrhachia, pleocytosis with lymphocytic predominance, negative gram stain, a bacterial culture and cytology. In addition, a complete metabolic panel revealed hyponatremia, elevated international normalized ratio and activated partial thromboplastin time, elevated total bilirubin and elevated inflammatory biomarkers. He was treated with a course of antibiotics and sent home. His symptoms continued to worsen and he presented to his local emergency department a week later and was again discharged home.
Approximately 1 week after this second discharge, he experienced a sudden onset of left facial and arm weakness with a reduced verbal output. He was able to follow commands during this time though. He presented to our institution and on arrival, he had begun to show a symptomatic improvement of the left face and arm weakness. On review of symptoms, he endorsed chills occurring daily at about 4 a.m. but denied fever, diaphoresis, numbness, tingling, dysphagia, dysarthria, visual disturbances, chest pain, shortness of breath, abdominal pain, or urinary symptoms. A neurological examination showed left lower motor neuron facial weakness with a House-Brackmann score of 2, dysarthria and diffuse hyperreflexia with bilateral Hoffmann's signs. Otherwise, the rest of his examination, including cranial nerves, was unremarkable.
The laboratory findings are summarized in the tables. Briefly, on initial presentation to our institution, a serum analysis revealed profound hyponatremia, mild normocytic anemia and mildly elevated inflammatory markers (table 1).
A spinal fluid analysis was repeated on initial presentation to our facility as well. His spinal fluid was grossly bloody with an elevated protein of 534 mg/dl and hypoglycorrhachia (glucose of 26 mg/dl). Blastomyces, coccidioides, histoplasma PCR and cryptococcus antigens were tested. Blastomyces PCR and cryptococcus antigen tests were negative. Initial coccidioides and histoplasma antibody screens were reactive, but reflex confirmatory tests for these pathogens were negative. Mycobacterium tuberculosis PCR, mycoplasma PCR and lyme PCR were all negative as well (table 2).
A repeat lumbar puncture 2 days after the initial presentation was less bloody, but remained hypercellular with 393 nucleated cells (46% lymphocytes). Protein and glucose levels similarly remained abnormal. Cytology and flow cytometry were performed on this sample and were negative. Histoplasma, blastomyces, and coccidioides PCR were again negative.
The analysis was broadened to include immunologic and paraneoplastic markers as shown in table 2. All immunologic and paraneoplastic markers were negative (table 2).
A brain MRI confirmed extensive nodular leptomeningeal enhancement along the left ventral medulla, and pons becoming more circumferential around the midbrain with disease extension into the left Sylvian fissure and along the pituitary infundibulum (fig. 1). A CT scan of the chest showed multiple small, noncalcified pulmonary nodules in the left upper and right lower lobes. There was no pleural effusion or adenopathy, and a whole-body FDG PET CT scan was negative. An abdominal CT demonstrated only a tiny hepatic cyst.
As the extensive workup remained inconclusive, the patient underwent a left far-lateral occipital craniotomy and C1 laminectomy with multiple biopsies of the brain stem and cerebellopontine angle with operative microscope and intraoperative stereotaxis. The arachnoid was thick with what appeared to be fungal colonies. These were sampled and a portion was removed and sent for pathology and cultures. Colonies were also noted to encompass the cerebellopontine angle, vertebral artery and cervical spinal accessory nerves. These were carefully dissected and multiple samples were sent off for pathological analysis. An example of an intraoperative mycotic mass is shown in figure 2.
Intraoperative samples included left medullary masses (1-4), CSF, C1 arachnoid, C1 arachnoid mass, C1 white matter, jugular foramen mass, subdural space at jugular tubercle swab, cervical spinal accessory mass, spinal cervical mass 1 and 2, tonsillar arachnoid (1-2), cervical medullary arachnoid 1 and 2. GMS and PAS stains of the tonsillar arachnoid No. 1 and left medullary mass No. 3 revealed necrotizing granulomatous inflammation with yeast forms, morphologically consistent with blastomyces. C1 arachnoid mass and jugular foramen mass swab ultimately grew blastomyces after 16 days of fungal culture. All other samples had negative GMS and PAS stains and did not grow organisms after 60 days of culture despite similar gross appearance to the positive samples. Fite stain for acid fast bacilli were negative on all samples.