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A Collection of Conditions Affecting the Brain

Volume 56 - Issue 5 - May 2016

Heparin-Induced Thrombocytopenia and Subdural Hematoma in Microangiopathic Antiphospholipid Syndrome

Sherif Nasef, MD, and Mansour Alghamdi, MBBS
King Fahad Specialist Hospital, Dammam, Saudi Arabia

The patient is a 38-year-old woman with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) that had been diagnosed in 2007. The diagnosis of APS was based on 3 consecutive first-trimester abortions and right-leg deep venous thrombosis (DVT), along with triple positivity of lupus anticoagulant, β2-glycoprotein I, and anticardiolipin antibodies in high titers. She had been anticoagulated with warfarin to a target international normalized ratio (INR) of 2 to 3, and warfarin was switched to subcutaneous heparin during her pregnancies.

History. While on warfarin and despite maintaining a target INR, the woman developed a second right-leg DVT in 2011. During that year, she had developed severe menorrhagia, with her hemoglobin dropping to 5.5 g/dL. She had been admitted to the hospital for blood transfusion and was found to have inferior vena cava thrombosis extending to both common iliac veins, with a platelet count of 30 × 103/µL. The menorrhagia was a result of the withdrawal of oral contraceptives, which she had used to stop her menses while performing the rites of Hajj.

In 2013, she was admitted to the hospital with acute shortness of breath, and a computed tomography (CT) pulmonary angiogram showed pulmonary embolism. She was discharged on warfarin 6 mg daily, azathioprine 100 mg daily, and prednisone 10 mg daily, but she stopped azathioprine on her own.

In 2015, she was hospitalized with fatigue, headache, and yellowish discoloration of her eyes. The headache was dull and was associated with nausea and vomiting. Past surgical history was positive for only dilation and curettage.

As for her social history, she is a housewife with no children after 10 abortions and/or miscarriages. She did not drink alcohol, smoke, or use illicit drugs. Her family history was significant for SLE in her niece.

Significant laboratory test results at that time included the following: platelet count, 24 × 103/µL; hemoglobin, 10.5 g/dL; lactate dehydrogenase, 580 U/L; creatinine, 3.7 mg/dL; INR above 10; and a peripheral blood film showing schistocytes and fragmented red blood cells, 1 to 4 per high-power field.


Figure 1. Noncontrast CT scan of the brain showing bilateral acute subdural hematoma.

 

CT of the brain (Figure 1) showed a posterior fossa subdural hematoma. The patient was admitted with a provisional diagnosis of thrombotic thrombocytopenic purpura (TTP) as opposed to catastrophic APS, and she received pulse corticosteroids, fresh frozen plasma, and intravenous immunoglobulin, 0.4 g/kg/d for 5 days due to the unavailability of plasma exchange. She then was transferred to our tertiary care center for further evaluation and management.

Physical examination. Upon arrival, her vital signs were normal. She was pale and icteric. Neck examination findings showed no jugular venous distension, lymphadenopathy, or goiter. Heart examination showed normal heart sounds with no murmurs. Chest examination revealed bilateral basal crackles. Her abdomen was soft and nontender, with no organomegaly or ascites. Her extremities showed 2+ pitting edema of the right foot. Neurologic and musculoskeletal examination findings were within normal limits.

Diagnostic tests. Laboratory test findings are shown in the Table. A chest radiograph showed pulmonary congestion. An echocardiogram showed a mildly dilated left ventricle, severely impaired systolic function with an ejection fraction of 20%, severe diastolic dysfunction with restrictive pattern, and pulmonary hypertension (pulmonary artery pressure, 53 mm Hg). Liver ultrasonography and renal Doppler ultrasonography showed patent hepatic and renal vessels.

Magnetic resonance imaging (MRI) of the brain showed bilateral posterior fossa subdural hematoma (Figure 2).

Treatment. A multidisciplinary team initiated management in the intensive care unit (ICU). The rheumatology team made the diagnosis of microangiopathic APS with concomitant subdural hematoma. The nephrologist diagnosed acute kidney injury due to either lupus nephritis or cardiorenal syndrome from the restrictive cardiomyopathy and recommended kidney biopsy to confirm lupus nephritis when the INR is lowered. Meanwhile, the nephrologist started her on prednisone and mycophenolate mofetil. The cardiologist initiated isosorbide dinitrate and hydralazine for cardiomyopathy. The neurosurgeon stated that the subdural hematoma required no surgical intervention. The hematologist recommended daily monitoring of INR off anticoagulants and placement of an inferior vena cava filter. The neurologist ordered MRI/magnetic resonance venography of the brain due to fluctuation of her level of consciousness; the results showed a stable subdural hematoma and no cerebral dural venous thrombosis.


Figure 2. MRI scan of the brain showing bilateral posterior fossa subdural hematoma.

 

The patient remained stable in the ICU for 4 days, with her creatinine level improving from 4.0 mg/dL to 2.2 mg/dL. She then was transferred to the general medical ward where she developed flash pulmonary edema. She was intubated and shifted back to the ICU on a heparin drip, broad-spectrum antibiotics, and IV furosemide. Bronchoscopy was done, and bronchoalveolar lavage culture results were negative for infections. The appearance of the lungs on chest radiographs improved after diuresis, and she was extubated within 72 hours; however, she was reintubated the next day for another attack of flash pulmonary edema.

Three days later, she was transferred to the general medical ward in stable condition, with normal oxygen saturation on room air and a normal chest radiograph. The heparin drip was switched to subcutaneous enoxaparin at renal-adjusted dose of 1 mg/kg/d. A central line was placed, and 2 sessions of plasma exchange were done, after which the creatinine level improved to 1.6 mg/dL and the bilirubin level normalized, but the platelet count dropped to 82 × 103/µL. Heparin-induced thrombocytopenia (HIT) was suspected and subsequently confirmed by HIT antibody test results.

Outcome of the case. The diagnosis of HIT was made in the setting of microangiopathic APS, complicated by subdural hematoma. Enoxaparin was stopped, and fondaparinux, 5 mg subcutaneously twice a day, was started. Follow-up echocardiography results showed an 11 × 7-mm thrombus at the tip of the central line, with some improvement of the diastolic function (Figure 3). The platelet count eventually normalized, and she was discharged home on rivaroxaban, 15 mg daily, due to difficulty with self-administration of fondaparinux at home. She was maintained on mycophenolate mofetil, prednisone, and spironolactone.

Figure 3. 2-D echocardiogram showing a moderate-sized, echodense,11 Å~ 7-mm thrombus, attached to the tip of the catheter.

 

Discussion. APS is diagnosed when a patient presents with thrombosis and/or pregnancy complications and with persistent serum antiphospholipid antibodies. The classification guidelines require meeting at least 1 clinical and 1 laboratory criterion.1

APS generally is characterized by thrombosis, but on rare occasions patients with the lupus anticoagulant directed against prothrombin may develop clinically important hypoprothrombinemia leading to hemorrhage.2 The reports of APS presenting with bleeding are rare. For example, adrenal hemorrhage was the cause of acute adrenal insufficiency in primary APS in 1 case study in 1998.3 Alveolar hemorrhage due to pulmonary capillary and microvascular thrombosis was reported in 5 patients with APS and may be the initial manifestation of the disease.4 Concomitant dysfunctional uterine bleeding and cerebral infarction were reported in 1 patient with APS.5 The cerebral infarction was considered to be induced by APS, hypovolemia due to massive bleeding, and oral contraceptive use.5

Serious intracerebral bleeding was the cause of death in 1 patient with APS who presented with left lower limb DVT.6 The thrombosis led to the diagnosis of SLE and secondary APS manifesting with renal vein thrombosis and diffuse alveolar and intracerebral hemorrhage. The diagnosis was catastrophic APS with an unusual combination of alveolar and intracerebral bleeding.6

Our patient was known to have APS manifesting with recurrent abortions, recurrent lower limb DVTs, pulmonary embolism, and inferior vena cava thrombosis. Her history was significant for an episode of heavy menorrhagia after withdrawal of oral contraceptives and an attack of subdural hematoma. Although the risk of potentially fatal intracranial bleeding is high in patients with APS and previous thrombosis treated with warfarin, the risk of thrombosis also is high.7

The presentation of our patient’s case was complex in that microangiopathic APS had overlapping features with TTP and catastrophic APS. The activity of ADAMTS-13 (a metalloprotease marker for TTP) was normal and Doppler ultrasonography of the liver and kidneys showed no evidence of thrombi, which left microangiopathic APS as the most probable diagnosis. The presence of subdural hematoma made the anticoagulation decision difficult. However, based on the risk-benefit balance, the decision was made to anticoagulate, because the subdural hematoma was stable in size on follow-up brain imaging. The diagnosis of HIT made the choices of anticoagulation rather limited and complicated the management. Fondaparinux was used while the patient was hospitalized, and rivaroxaban was used after discharge.

The association between APS and HIT has been rarely reported in the literature. The conditions share some similarities, such as thrombocytopenia and hypercoagulability with arterial and venous thrombosis.8 The presence of both conditions in our patient was likely to be missed if such an association had not been considered.

References:

  1. Keeling D, Mackie I, Moore GW, Greer IA, Greaves M; British Committee for Standards in Haematology. Guidelines on the investigation and management of antiphospholipid syndrome. Br J Haematol. 2012;157(1):47-58.
  2. Jayachandran NV, Rajasekhar L, Narsimulu G, Prasad V. Antiphospholipid antibody syndrome presenting with disseminated bleeding and spinal subdural hemorrhage. Spinal Cord. 2007;45(11):753-755.
  3. Caron P, Chabannier M-H, Cambus J-P, Fortenfant F, Otal P, Suc J-M. Definitive adrenal insufficiency due to bilateral adrenal hemorrhage and primary antiphospholipid syndrome. J Clin Endocrinol Metab. 1998;83(5):1437-1439.
  4. Gertner E. Diffuse alveolar hemorrhage in the antiphospholipid syndrome: spectrum of disease and treatment. J Rheumatol. 1999;26(4):805-807.
  5. Yoshidome Y, Morimoto S, Tamura N, et al. A case of primary antiphospholipid antibody syndrome presenting with dysfunctional uterine bleeding and cerebral infarction. Mod Rheumatol. 2007;17(3):251-252.
  6. Boura P, Papadopoulos S, Tselios K, et al. Intracerebral hemorrhage in a patient with SLE and catastrophic antiphospholipid syndrome (CAPS): report of a case. Clin Rheumatol. 2005;24(4):420-424.
  7. Ruiz-Irastorza G, Khamashta MA, Hunt BJ, Escudero A, Cuadrado MJ, Hughes GRV. Bleeding and recurrent thrombosis in definite antiphospholipid syndrome: analysis of a series of 66 patients treated with oral anticoagulation to a target international normalized ratio of 3.5. Arch Intern Med. 2002;162(10):1164-1169.
  8. Hoppensteadt DA, Walenga JM. The relationship between the antiphospholipid syndrome and heparin-induced thrombocytopenia. Hematol Oncol Clin North Am. 2008;22(1):1-18.

 

Cerebral Aspergillosis in an Immunocompetent Man

Karina Mill, MSIV, and Stephen Winfield, MD
Saba University School of Medicine, Saba, Dutch Caribbean

Andrew Rosenthal, MD
Memorial Regional Hospital, Hollywood, Florida

A 69-year-old man presented to the emergency department with a 4-month history of headaches and right-eye vision loss that had been worsening over the past week. He was neurologically intact, with a Glasgow Coma Score (GCS) of 15. The patient denied nausea, vomiting, fever, chills, shortness of breath, chest pain, cough, or any other associated symptoms. His medical history was positive for type 2 diabetes mellitus and hypothyroidism, and his vaccination history was unknown. Upon admission, the patient was immunologically intact and HIV-negative with no neutropenia.

Early differential diagnosis included temporal arteritis (TA), for which he was started on high-dose corticosteroids. TA later was ruled out with biopsy. Magnetic resonance imaging (MRI) of the brain revealed a right posterior eye mass surrounding the right optic nerve and extending into the brain, involving the right carotid artery (Figure 1).


Figure 1. Brain MRI showing abnormal enhancement around the right optic nerve and involving the inferior aspect of the right frontal lobe.

 

The patient underwent immediate right frontal craniotomy with debridement of the mass and biopsies of the brain and maxillary sinuses. Postoperatively, the patient was alert and oriented, with a GCS of 15. Brain biopsy results were positive for the presence of Aspergillus fumigatus; sinus biopsy results were positive for Haemophilus influenzae, coagulase-negative staphylococcus, and fungal hyphae branching at 45° angles.

The patient was started on ceftriaxone to cover H influenzae, along with voriconazole and micafungin, and was admitted to the intensive care unit (ICU).

Three days postoperatively, the patient’s neurologic condition began to worsen. He lost vision in his right eye completely. His mental status deteriorated to a GCS of 6. Computed tomography (CT) with contrast revealed a right temporal and basal ganglia cerebral vascular accident with associated left hemiparesis. Fifteen days later, he sustained a new stroke involving the right posterior temporal and occipital lobes (Figure 2). Transesophageal echocardiography ruled out a cardiac source. CT angiogram revealed a ruptured mycotic aneurysm and resulting subarachnoid hemorrhage. He underwent right middle cerebral artery angioplasty and flow diversion. The patient went into respiratory failure postoperatively and required intubation and ventilator placement.


Figure 2. Brain CT revealing acute posterior right temporal, parietal, and occipital infarcts with moderate hydrocephalus.

 

Discussion. Aspergillosis is a rare fungal infection that typically presents in severely immunocompromised patients who have received an organ transplant or are receiving chemotherapy. Corticosteroid use is an additional risk factor.1 Aspergillosis typically infects the lungs or the sinuses, but invasive disease has been well described. Cerebral aspergillosis can develop by hematologic dissemination, direct extension from a sinus infection, or by direct inoculation of the brain via trauma or surgery.2,3

Rare cases of cerebral aspergillosis have been described in immunocompetent patients.4-9 These patients often have comorbidities such as diabetes, have had extended hospital or ICU stays, or have had recent corticosteroid treatment. The prognosis for cerebral aspergillosis is poor, and the condition is associated with high mortality rates, exceeding 90% in critically ill patients.10 Survival is improved in immunocompetent patients as a result of improved immune response and treatment options.11

Mycotic aneurysms are a devastating and life-threatening complication of cerebral aspergillosis that may rupture and result in hemorrhage. Treatment consists of a combination of antifungal medication, notably voriconazole and echinocandins, which have replaced amphotericin B due to its adverse effects and poor central nervous system penetration.10,12,13 Surgical resection, when possible, improves patient outcomes and prevents neurological complications.14

Clinical features of cerebral aspergillosis are nonspecific but can be dramatic. Identifying the infection early is a critical, and prophylactic antifungal medication should be administered when there is a high suspicion of an intracranial infection. Early administration of antibiotics and antifungals in a suspected cerebral abscess improves patient outcomes.1,7 Imaging studies reveal an intracranial mass, and laboratory results reveal an increased white blood cell count and positive cultures.15-17 Definitive diagnosis requires a histopathologic staining.12

Empiric treatment of a suspected intracranial fungal infection includes amphotericin B. Baseline renal function requires assessment, since amphotericin B is renotoxic.12 Treatment of confirmed aspergillosis includes voriconazole and an echinocandin (eg, micafungin). Combination therapy generally is preferred to voriconazole alone, because it has been shown to improve survival.18 Voriconazole is used because it is one of the few antifungal agents that are able to penetrate the central nervous system and reach appropriate inhibitory concentrations.10,13 In patients receiving hematopoietic cell transplantation, glucocorticoid use has been associated with higher mortality rates.19-21 Diabetes also has been reported as a comorbid condition in numerous reported cases of cerebral aspergillosis in immunocompetent patients.5,22-24 Given that our patient had a positive past medical history of diabetes and had received a short course of glucocorticoids for suspected temporal arteritis, this relationship may be stronger than previously had been postulated. Further studies are warranted.

References:

  1. Gubler C, Wildi SM, Imhof A, Schneemann M, Müllhaupt B. Disseminated invasive aspergillosis with cerebral involvement successfully treated with caspofungin and voriconazole. Infection. 2007;35(5):364-366.
  2. Hoenigl M, Krause R. Antifungal therapy of aspergillosis of the central nervous system and Aspergillus endophthalmitis. Curr Pharm Des. 2013;19(20): 3648-3668.
  3. Segal BH. Aspergillosis. N Engl J Med. 2009;360(18):1870-1874.
  4. Bokhari R, Baeesa S, Al-Maghrabi J, Madani T. Isolated cerebral aspergillosis in immunocompetent patients. World Neurosurg. 2014;82(1-2):e325-e333.
  5. Kim DG, Hong SC, Kim HJ, et al. Cerebral aspergillosis in immunologically competent patients. Surg Neurol. 1993;40(4):326-331.
  6. Shamim MS, Enam SA, Ali R, Anwar S. Craniocerebral aspergillosis: a review of advances in diagnosis and management. J Pak Med Assoc. 2010;60(7): 573-579.
  7. Lee J-C, Lim D-J, Ha S-K, Kim S-D, Kim S-H. Fatal case of cerebral aspergillosis: a case report and literature review. J Korean Neurosurg Soc. 2012; 52(4):420-422.
  8. Koshy R, Malhotra P. Treatment of primary aspergilloma of the central nervous system in a diabetic immunocompetent patient with surgical resection and voriconazole: a case report and review of the literature. Turk Neurosurg. 2011;21(4):641-644.
  9. Phuttharak W, Hesselink JR, Wixom C. MR features of cerebral aspergillosis in an immunocompetent patient: correlation with histology and elemental analysis. AJNR Am J Neuroradiol. 2005;26(4):835-838.
  10. Schwartz S, Thiel E. Cerebral aspergillosis: tissue penetration is the key. Med Mycol. 2009;47(suppl 1):S387-S393.
  11. Ehrmann S, Bastides F, Gissot V, et al. Cerebral aspergillosis in the critically ill: two cases of successful medical treatment. Intensive Care Med. 2005; 31(5):738-742.
  12. Ruhnke M, Kofla G, Otto K, Schwartz S. CNS aspergillosis: recognition, diagnosis and management. CNS Drugs. 2007;21(8):659-676.
  13. Herbrecht R, Denning DW, Patterson TF, et al; Invasive Fungal Infections Group of the European Organisation for Research and Treatment of Cancer; Global Aspergillus Study Group. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002;347(6):408-415.
  14. Kourkoumpetis TK, Desalermos A, Muhammed M, Mylonakis E. Central nervous system aspergillosis: a series of 14 cases from a general hospital and review of 123 cases from the literature. Medicine (Baltimore). 2012;91(6): 328-336.
  15. McCarthy M, Rosengart A, Schuetz AN, Kontoyiannis DP, Walsh TJ. Mold infections of the central nervous system. N Engl J Med. 2014;371(2):150-160.
  16. Sidani C, Freiser ME, Saigal G, Sklar E. Unusual case of cerebral aspergillosis with clinical and imaging findings mimicking lymphoma. Neuroradiol J. 2013;26(3):290-296.
  17. Soeffker G, Wichmann D, Loderstaedt U, Sobottka I, Deuse T, Kluge S. Aspergillus galactomannan antigen for diagnosis and treatment monitoring in cerebral aspergillosis. Prog Transplant. 2013;23(1):71-74.
  18. Marr KA, Schlamm HT, Herbrecht R, et al. Combination antifungal therapy for invasive aspergillosis: a randomized trial. Ann Intern Med. 2015;162(2): 81-89.
  19. Upton A, Kirby KA, Carpenter P, Boeckh M, Marr KA. Invasive aspergillosis following hematopoietic cell transplantation: outcomes and prognostic factors associated with mortality. Clin Infect Dis. 2007;44(4):531-540.
  20. Nivoix Y, Velten M, Letscher-Bru V, et al. Factors associated with overall and attributable mortality in invasive aspergillosis. Clin Infect Dis. 2008;47(9): 1176-1184.
  21. Baddley JW, Andes DR, Marr KA, et al. Factors associated with morality in transplant patients with invasive aspergillosis. Clin Infect Dis. 2010;50(12): 1559-1567.
  22. Pellacchia V, Terenzi V, Moricca LM, Buonaccorsi S, Indrizzi E, Fini G. Brain abscess by mycotic and bacterial infection in a diabetic patient: clinical report and review of literature. J Craniofac Surg. 2006;17(3):578-584.
  23. Liu X, Lin W, Wang Y, Wang Z, Du Y. A fatal case of cerebral aspergillosis in a diabetes mellitus patient. Neurol Sci. 2015;6(9):1717-1719.
  24. Li W, Shafi N, Periakaruppan R, Valyi-Nagy T, Groth J, Testai FD. Cerebral aspergillosis in a diabetic patient leading to cerebral artery occlusion and ischemic stroke: a case report and literature review. J Stroke Cerebrovasc Dis. 2015;24(1):e39-e43.

 

Creutzfeldt-Jakob Disease

John Prater and Scott G. Turner, MD
Geisinger Medical Center, Danville, Pennsylvania

A 72-year-old woman with a past medical history of depression, hyperlipidemia, and autoimmune liver disease presented to the emergency department with a 6-week history of new onset and progressive confusion, memory dysfunction, and unsteady gait. Her husband reported that she had been in good health as of 2 months prior, going on regular walks and easily holding conversations with family.

At the time of presentation, she was nonverbal or responded only with 1-word answers, she did not recognize her family members, and she had difficulty walking, with a significant gait disturbance. She had no recent history of illness or head trauma, and no history of having had a stroke, seizure, or other neurologic disease.


Figure 1. The woman’s MRI showed symmetric restricted diffusion throughout the cortex of bilateral cerebral hemispheres, most pronounced in the parietal occipital regions.

 

Physical examination. Her vital signs were unremarkable, with a blood pressure of 134/63 mm Hg, a temperature of 36.6°C, a pulse of 79 beats/min, and a respiratory rate of 16 breaths/min. On neurologic examination, she did not speak or follow commands, but occasionally smiled and tracked the examiner across the room, suggestive of akinetic mutism. Myoclonus was noted at the head and upper extremities.

Diagnostic tests. An extensive laboratory workup for causes of encephalopathy was performed. Levels of thyroid-stimulating hormone, vitamin B12, folic acid, and ceruloplasmin were normal, and results of a cytomegalovirus test, Lyme disease titer, cryptococcal antigen/culture, and a paraneoplastic panel were negative.

On magnetic resonance imaging (MRI) scans of the brain, diffuse and symmetric high-signal abnormality in the cortex of both cerebral hemispheres was noted, most pronounced in the parietal/occipital region (Figure 1). An electroencephalogram (EEG) showed a diffuse disturbance of cerebral function manifested by generalized background slowing, coupled with periodic sharp wave complexes in a generalized distribution (Figure 2).

The patient’s clinical presentation and MRI scans and EEG findings were consistent with the diagnosis of Creutzfeldt-Jakob disease (CJD). Therefore, a cerebrospinal fluid (CSF) protein 14-3-3 study was done by way of a lumbar puncture, and levels of CSF protein 14-3-3 were found to be elevated.


Figure 2. The EEG showed periodic sharp wave complexes (arrows).

 

Discussion. CJD belongs to a family of prion diseases known as transmissible spongiform encephalopathies. It was first recognized as a disease entity in the early 1920s.1 CJD is seen primarily as a neurodegenerative disease, but it also can demonstrate infectious features by transfer of neuronal tissue from one patient to another.2 This progressive disorder may worsen on an almost daily basis3 and has a 100% fatality rate because of its unconventional proteinaceous causative agent, the prion.1

Prions are misfolded forms of a protein normally found within the brain.4 They have the ability to propagate themselves by promoting conformational changes of the normal prion protein via an autocatalytic amplification mechanism.3,4 This misfolded protein is insoluble and resistant to protease degradation and thus tends to accumulate in tissues.3 The neuropathologic result is a characteristic neuronal loss, spongiform degeneration, and reactive astrogliosis (scar formation).1

The worldwide annual incidence of CJD is estimated to be 1 case per 1 million population, with the rate highest in people between 60 and 75 years of age.5 Patients present with rapidly progressive dementia accompanied by other neurologic features such as myoclonus, akinetic mutism, and ataxia.3,6

There is no simple, noninvasive diagnostic test for CJD in living persons, and definitive diagnosis requires brain biopsy. Nevertheless, a highly probable diagnosis can be made using typical clinical features and 3 investigatory paths: EEG, MRI, and 14-3-3 protein detection in CSF.3 EEG results typically show background slowing and periodic sharp wave complexes (biphasic or triphasic).7 MRI of the brain usually shows hyperintense lesions on diffusion-weighted imaging in at least 2 cortical regions, or in the caudate nucleus or putamen, representing the pathologic spongiform changes.6,8 For patients in whom CJD is strongly suspected, CSF 14-3-3 protein assay can be helpful in supporting the diagnosis.5

Outcome of the case. Because the woman met the criteria consistent with a highly probable diagnosis of CJD, the family decided against a brain biopsy. Due to the rate of clinical decline, the poor prognosis, and the lack of treatment, hospice care was elected.

References:

  1. Lee J, Hyeon JW, Kim SY, Hwang K-J, Ju YR, Ryou C. Review: laboratory diagnosis and surveillance of Creutzfeldt-Jakob disease. J Med Virol. 2014; 87(1):175-186.
  2. Karch A, Raddatz LM, Ponto C, Hermann P, Summers D, Zerr I. Diagnostic profiles of patients with late-onset Creutzfeldt-Jakob disease differ from those of younger Creutzfeldt-Jakob patients: a historical cohort study using data from the German National Reference Center. J Neurol. 2014;261(5):877-883.
  3. Knight R. Creutzfeldt-Jakob disease: a rare cause of dementia in elderly persons. Clin Infect Dis. 2006;43(3):340-346.
  4. Degnan AJ, Levy LM. Neuroimaging of rapidly progressive dementias, part 2: prion, inflammatory, neoplastic, and other etiologies. AJNR Am J Neuroradiol. 2014;35(3):424-431.
  5. Muayqil T, Gronseth G, Camicioli R. Evidence-based guideline: diagnostic accuracy of CSF 14-3-3 protein in sporadic Creutzfeldt-Jakob disease: report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2012;79(14):1499-1506.
  6. Zerr I, Kallenberg K, Summers DM, et al. Updated clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease. Brain. 2009;132(pt 10):2659-2668.
  7. Ayyappan S, Seneviratne U. Electroencephalographic changes in sporadic Creutzfeldt-Jakob disease and correlation with clinical stages: a retrospective analysis. J Clin Neurophysiol. 2014;31(6):586-593.
  8. Gao T, Lyu J-H, Zhang J-T, et al. Diffusion-weighted MRI findings and clinical correlations in sporadic Creutzfeldt-Jakob disease. J Neurol. 2015;262(6): 1440-1446.