A 29-year-old woman with no known past medical history is admitted to the ICU with status epilepticus. Her family reports that she complained of headaches, fevers, and myalgias that started a few days prior to presentation. On exam, you notice abnormal movements of her lips and mouth, but no evidence of seizure activity on EEG. A brain MRI is unremarkable. CSF obtained via lumbar puncture was notable for 14 WBCs, no RBC, mildly elevated protein, and normal glucose. CSF culture is negative and PCR for HSV is also negative. Anti-NMDA antibody in the CSF and serum is positive.
What is the MOST appropriate next step to make a diagnosis?
Correct Answer: D
The patient described has an anti-NMDA receptor antibody–mediated encephalitis. The usual presentation is subacute (3 months) progressive neurological symptoms, which could include new psychiatric symptoms, movement disorders, and new onset seizures. MRI will characteristically show T2 abnormalities, but these are not necessary for the diagnosis. Imaging is needed more for exclusion of other causes (option A is incorrect). The CSF profile could be consistent with primary CNS malignancies; however, CNS malignancies are usually accompanied by specific imaging findings, and not by a positive anti- NMDA receptor antibody (option B is incorrect). As part of the autoimmune encephalitis workup, it is important to rule out systemic autoimmune diseases. However, in this specific case, there are no other signs or symptoms of SLE, and the patient has marker for autoimmune encephalitis (option C is incorrect).
Anti-NMDA receptor encephalitis is the first specific autoantibody described for CNS paraneoplastic syndrome. The most common associated neoplasm, especially given the young age, is an ovarian teratoma (option D is correct).
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A 52-year-old woman with past medical history of infiltrating lobular carcinoma of the breast status post left mastectomy and neoadjuvant chemotherapy is brought to the ER by her family, reporting a 3-day history of headaches, nausea, vomiting, diplopia, and a witnessed fall prior to presentation. Neurological examination is notable for medial deviation of the right eye and inability to completely close the eyes. Lumbar puncture is performed and while waiting for the results, a brain MRI is obtained, which is notable for diffuse leptomeningeal contrast enhancement of the cortical surface and the basal cisterns along the ventral surface of the brainstem.
What is the CSF profile most consistent with this patient’s presentation?
Correct Answer: A
The patient in the aforementioned scenario is presenting with leptomeningeal carcinomatosis (LM). CSF findings are characterized by elevated protein count, low glucose count, and lymphocytic pleocytosis. LM is defined by the spread of tumor to the arachnoid and pia mater (leptomeninges) as opposed to the dura mater and is diagnosed in 5% of patients with metastatic cancer. The most common solid tumors associated with LM are breast CA, lung CA, melanoma, and cancers of the GI tract. Patients often present with multifocal neurological signs and symptoms, including headaches, nausea/vomiting, and neck pain or stiffness, etc., which may indicate increased intracranial pressure and/or meningeal irritation. Other symptoms may include diplopia, facial weakness, sensorineural hearing loss, and dysphagia or dysarthria, which indicate invasion of cranial nerves. Gait instability, falls, and dizziness can result from brainstem invasion.
LM is suspected in patients presenting with multilevel neurological findings and diagnosis is confirmed by brain MRI and CSF analysis. Brain MRI is notable for diffuse leptomeningeal contrast enhancement. Prominent CSF findings include elevated protein count, low glucose count, and lymphocytic pleocytosis (option A is correct). Elevated protein, low glucose, and neutrophilic pleocytosis are consistent with findings in patients with bacterial meningitis (option B is incorrect). Normal to elevated protein count, with normal glucose count, and lymphocytic pleocytosis is consistent with viral meningitis (option C is wrong). Mildly elevated protein, normal glucose, and normal WBC count is consistent with CSF finding in patients with multiple sclerosis (option D is wrong).
A 72-year-old man with past medical history of hypertension and prostate cancer status post radiation therapy is brought to ED after sustaining a witnessed mechanical fall. He denies loss of consciousness and reports that his head did not hit the floor. He reports a 3-week history of progressive lower back pain radiating down his left leg. The day before he experienced two episodes of fecal incontinence. A head CT is negative for any acute abnormalities. MRI spine shows collapsed L2 -L4 lumbar vertebrae and a mass invading the spinal cord with surrounding vasogenic edema.
What is the most appropriate next step in management?
Correct Answer: C
The patient described in the scenario above has spinal cord compression due to metastatic disease and should receive steroids. In addition, analgesics should be administered and the patient should undergo rest and appropriate immobilization to protect vulnerable spine segments from further damage.
Vertebral metastases occur in up to 3% to 5% of patients with a diagnosis of cancer and can be the presenting symptom. Back pain is the most common feature and occurs in up to 95% of the patients with metastatic spinal cord compression syndrome. It is more commonly radicular in nature but can be localized, particularly to mid- and high thoracic spinal areas. While radiation therapy and/or surgical resection are considered definitive treatment, randomized trials support the use of steroids as beneficial adjunctive therapy in patients with myelopathy from spinal cord compression while planning for definitive therapy. Steroids are contraindicated in patients who are suspected to have lymphoma as the underlying cause of spinal cord compression.
A 46-year-old patient with a history of known glioblastoma multiforme of the right temporal lobe has a witnessed seizure. He is now postictal and lethargic. A head CT is performed which reveals a heterogeneous mass with hemorrhage into the tumor and a large amount of vasogenic edema leading to mass effect on the midbrain. After his postictal period has resolved,
which set of clinical findings would be most suggestive of uncal herniation?
Correct Answer: B
Compression (torquing) of the outer fibers of third cranial nerve, compression of ipsilateral corticospinal tract, and the resulting effects on the reticular activating system define brain herniation syndrome. Uncal herniation is a dynamic process in which the uncus or a portion of the anterior temporal lobe prolapses into the hiatus encircled by the tentorium cerebelli. As the uncus herniates into this space, it compresses the midbrain first, resulting in ipsilateral third nerve palsy. When the lesion is cortical and unilateral, pupillary abnormalities manifest on the same side as the lesion. Contralateral weakness or hemiplegia occurs secondary to transtentorial herniation.
Option C is incorrect because it represents left-sided uncal herniation or a Kernohan notch syndrome (false localizing sign) from a right-sided lesion. Imaging is not required for diagnosis of the clinical syndrome, but it does provide supporting evidence.
Cerebral herniation is a “brain code”—life-threatening neurological emergencies indicating that intracranial compliance adaptive mechanisms have been overwhelmed. Cerebral herniation is initially treated with hyperventilation and osmotherapy. Additional therapeutic measures which might be considered for this case include administration of dexamethasone for vasogenic edema, CSF drainage to reduce intracranial pressure, pharmacological reduction of cerebral metabolic rate, decompressive hemicraniectomy, and intraoperative tumor debulking.
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