Pseudo-Pseudotumor Cerebri (radiology)

Imaging of the spine was recommended. The abnormal CSF suggested a meningeal process, and we had no explanation for what seemed to be bilateral papilledema. The two LPs were technically difficult and painful and we were concerned about a spinal cord/spinal meningeal neoplasm. Spinal imaging was not done and instead, his evaluation focused on looking for evidence of lymphoma (because of the few plasmacytoid/plasmablasts seen on first LP). A repeat LP under fluoroscopy (07/31/2015), which was again difficult and painful, showed CSF-OP 24cm, only 1cc of CSF was obtained and sent to pathology; cytology was negative. His symptoms did not improve. Repeat SPEP was unchanged. CBC showed mildly elevated WBC. He had normal chest/abdomen/pelvis CT (05/26/2015), hematology evaluation (08/12/2015) followed by a bone marrow biopsy (09/03/2015), bone survey, chest X-Ray, whole body PET-CT (09/02/2015). Ophthalmologic examination (09/10/2015) was unchanged with persistent bilateral disc edema and stable VF. He still complained of severe headaches and fluctuating vision. He mentioned episodic unusual feeling in his legs with episodes during which he was not able to walk normally. MRI of the entire spine with contrast showed diffuse leptomeningeal enhancement involving the entire spine, worse at the lumbar and sacral levels, where there was circumferential thickened leptomeningeal enhancing soft tissue occupying the thecal sac. Repeat brain MRI with contrast showed mild leptomeningeal enhancement at the skullbase. The patient was admitted to the hospital and a biopsy of the mass at the L2 level was performed via posterior laminectomy. Pathology showed a leptomeningeal melanocytic neoplasm, consistent with a malignant melanoma.1 He had no prior skin melanoma and repeat CT of chest/abdomen/pelvis was normal. Molecular studies were negative for BRAF, GNAQ and GNA11 mutations,2 but showed alteration in the RIPK1 gene which has been recently described as a driver in melanoma.

 No relevant disclosures  54 yo white man  Type II diabetes mellitus Hypothyroidism   Stung by a bee (neck)  Headaches and blurry vision  Ophthalmologist: ▪ Normal visual acuity ▪ Bilateral optic disc edema  Brain/orbits MRI (contrast)  Syphilis, Lyme, TSH, ANA, ESR: neg/normal  Neurologist:  Normal examination  Blood pressure normal; BMI: 30kg/m2  Brain/orbits MRI (contrast)  Ophthalmologist:  Normal visual acuity  Bilateral optic disc edema  MRA/MRV (contrast)  Arachnoid granulation     (left transverse sinus) No stenosis of right transverse sinus No venous thrombosis MRA normal No dural fistula  Lumbar puncture (traumatic and painful)  Pressure: 12 cm H2O  CSF: hazy, pink  124 white cells (32% neutrophils, 66% lymphocytes)  22599 red cells  Glucose 104mg/dl  Protein >300mg/dl  Cytology negative; a few plasmacytoids/plasmablasts (blood contamination)  Serum protein electrophoresis:  Mild hypogammaglobulinemia   Headaches improved Diagnosis of "pseudotumor cerebri"  Acetazolamide 500mg x2/day ▪ => Vomiting ▪ Acetazolamide discontinued  Ophthalmologist:  Normal visual acuity  Bilateral papilledema  Neurologist:  Normal examination  Lumbar puncture (traumatic and painful) (fluoroscopy)  Pressure: 25.8 cm H2O  CSF: clear; xanthochromia +  90 white cells (90% neutrophils)  288 red cells  Glucose 100mg/dl; Protein <6mg/dl  Cytology negative  Headaches improved  Neuro-ophthalmology end of June 2015  Stable examination Which of the following tests was ordered at this point? 1. Arterial Cerebral Catheter Angiogram 2. Cerebral Venogram with Manometry 3. Repeat Lumbar Puncture 4. MRI of the Spine  Instead, patient seen in hematology (because LP April 2015: "a few plasmacytoids / plasmablasts")  Repeat lumbar puncture: traumatic and painful ▪ Pressure 24 cm H2O ▪ 1cc CSF: cytology negative  Bone marrow biopsy: normal  Chest X ray: normal  Bone survey  PET-CT whole body: normal  Neuro-ophthalmology:  Severe headaches  Visual acuity normal  Bilateral papilledema  Unusual feeling in both legs  Sometimes, does not know where his feet are Which of the following tests needs to be ordered? 1. Arterial cerebral catheter angiogram 2. Cerebral venogram with manometry 3. Repeat lumbar puncture 4. MRI of the Spine T2 T1 T1 Fat Sat with contrast H&E, 40x H&E, high magnification S100 Melan A HMB45 The ki-67 proliferation index was elevated and approximated 7-8%  Primary  Molecular studies:  BRAF and GNAQ/GNA11 mutations negative ▪ Next Generation Sequencing (26 genes)  Cytogenomic microarray (SNP) ▪ Gain of the distal portion of chromosome 6p ▪ Alteration in the gene RIPK1 ("oncogenic driver" in melanoma) Cancer Res. 2015 Apr 15;75(8):1736-48  Intracranial hypertension with headaches and papilledema for 14 months!  Diagnosis of "pseudotumor cerebri" suggested despite abnormal CSF  Pitfalls => Delayed diagnosis  "Traumatic" lumbar punctures  Lack of neurologic symptoms/signs (14 months)   CSF analysis:  Necessary to make a diagnosis of idiopathic intracranial hypertension  CSF must be completely normal! Unexplained bilateral papilledema: think about spinal cord tumors  Even when CSF is normal  Even without neurologic symptoms/signs  Penetration of blood into the CSF during a traumatic LP falsely elevates white cells and protein =>Estimate false increase based on CSF red cells number CSF White Cell Count CSF Protein Count Increased by: 1WC for 750RC Increased by: 1 g protein for 100 000 RC  Lumbar puncture (traumatic and painful)  Pressure: 12 cm H2O        Traumatic LP: 1 white cell for every 750 red cells CSF: hazy, pink 124 white cells (32% neutrophils, lymphocytes) 22,59966% red cells / 750 = 30 white cells 22,599 red cells Traumatic LP: Glucose 104mg/dl 1 mg per dL (0.01 g per L) of Protein >300mg/dl protein for each 1,000 red cells Cytology negative; a few plasmacytoids/plasmablasts (bloodred contamination) 1 g protein for 100,000 cells Serum protein electrophoresis:  Mild hypogammaglobulinemia 22,599 red cells / 1,000 = 22mg   Dissemination of tumor cells Elevated CSF protein and protein degradation products  => CSF obstruction (decreased CSF absorption)  Literature: >60% of cases had elevated protein level ▪ CSF protein 38-10,500mg/dl; >100mg/dl in 66% of 54 cases  When no increased protein  ?Compromise of the lumbosacral elastic reservoir