Journal of Medical Cases, ISSN 1923-4155 print, 1923-4163 online, Open Access
Article copyright, the authors; Journal compilation copyright, J Med Cases and Elmer Press Inc
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Case Report

Volume 9, Number 9, September 2018, pages 296-302

A Rare Case of Paraneoplastic Encephalitis in Association With Breast Cancer


Figure 1.
Figure 1. (a) MRI of brain with and without contrast showing T2/FLAIR hyperintensity along the medial temporal lobe involving portions of the hippocampus and amygdala. (b) CT of chest with contrast showing markedly enlarged axillary lymph nodes. (c) Ultrasound of right breast and axilla showing 4 × 4 × 3 mm hypoechoic lobulated nodule at 2 o’clock axis. (d) MRI of bilateral breast with and without contrast showing clumped enhancement in the upper outer quadrant of the right breast. (e) MRI of bilateral breast with and without contrast showing a small 8 mm area of patchy non-mass enhancement in the lower outer right breast.


Table 1. Laboratory Data
TestResultsReference range
Workup for neuropathy and encephalitis
  Vitamin B12760193 - 986 ng/dL
  Folic acid65.74 - 18 ng/mL
  TSH0.860.340 - 4.820 µIU/mL
  Homocysteine8.65.0 - 12.0 µmol/L
  Gliadin IgAb9.0Negative < 20
  Ganglioside antibody panelNegative
  Zinc0.730.66 - 1.10 µg/mL
  Erythrocyte sedimentation rate270 - 30 mm/h
  Rapid plasma regainNon-reactive
  Lyme disease antibody, serum0.02< 0.90 index
  Blood parasitesNegative
  Epstein-Barr virus antibody panelNegative
  Spotted fever antibody IgG, IgA, IgMNegative
  Bartonella antibody panelNegative
  Ehrlichia antibody panelNegative
  Babesia microti antibody IgG, IgMNegative
  Antinuclear antibody (ANA)Positive 1:640 speckled
  ANA reflex antibodiesNegative
  Rheumatoid factor< 100 - 15 IU/mL
  Cardiolipin antibody IgA, IgG, IgMNegative
  Neuromyelitis optica NMO/Aqua4-IgGNegative
Heavy metals screen, serum
  Arsenic2.00 - 12 ng/mL
  Lead< 1.00.0 - 4.9 µg/mL
  Mercury< 1.00.0 - 9.0 ng/mL
  Cadmium0.20.0 - 4.9 ng/mL
  Copper1.360.75 - 1.45 µg/mL


Table 2. Cerebrospinal Fluid Analysis
CSFResultsReference range
*CSF IgG index: CSF IgG to CSF albumin ratio compared to the serum IgG to serum albumin ratio. An increase in the index is an indicator of IgG production in the central nervous system. In our patient serum albumin 3.5 g/dL and serum IgG 814 mg/dL (Reference:
WBC440 - 5/UL
RBC< 1,000/UL
Glucose11040 - 70 mg/dL
Protein5812 - 60 mg/dL
CytologyNegative for malignant cells
Oligoclonal bands14< 4 bands
IgG index, CSF*1.22≤ 0.85
IgG9.4≤ 8.1 mg/dL
Albumin33.9≤ 27.0 mg/dL
IgG/albumin0.28≤ 0.21
Synthesis rate28.77≤ 12 mg/24 h
Meningitis/encephalitis panel, PCR
  Escherichia coli K1Not detected
  Hemophilus influenzaeNot detected
  Listeria monocytogenesNot detected
  Neisseria meningitidisNot detected
  Streptococcus agalactiaeNot detected
  Streptococcus pneumoniaeNot detected
  CytomegalovirusNot detected
  EnterovirusNot detected
  Herpes simplex virus 1 and 2Not detected
  Human herpesvirus 6Not detected
  Varicella zoster virusNot detected
  Cryptococcus neoformans/gattiNot detected
Paraneoplastic panel
  Amphiphysin antibody1: 15,360< 1:240 titer
  ANNA-1, SNegative< 1:240 titer
  ANNA-2, SNegative< 1:240 titer
  ANNA-3, SNegative< 1:240 titer
  AGNA-1, SNegative< 1:240 titer
  PCA-1, SNegative< 1:240 titer
  PCA-2, SNegative< 1:240 titer
  PCA-TR, SNegative< 1:240 titer
  CRMP-5-IgGNegative< 1:240 titer
  Striated muscle AbNegative< 1:120 titer
  P/Q-type calcium channel AbNegative≤ 0.02 nmol/L
  N-type calcium channel AbNegative≤ 0.03 nmol/L
  Ach receptor binding AbNegative≤ 0.02 nmol/L
  ACHR ganglionic neuronal Ab, SNegative≤ 0.02 nmol/L
  Neuronal (V-G) K+ channel Ab, SNegative≤ 0.02 nmol/L
  GAD65 Ab assay, SNegative≤ 0.02 nmol/L


Table 3. Clinical Features and Investigations Associated With Various PNS [5]
SyndromeClinical featureInvestigations
Paraneoplastic encephalomyelitis (PEM)Subacute involvement of more than one area of the CNS includes cortical, limbic or brainstem encephalitis, cerebellar dysfunction, myelitisMRI of the relevant part. CSF - pleocytosis, elevated protein and oligoclonal bands
Limbic encephalitis (LE)Memory problems, seizures, mood and sleep abnormalitiesMRI brain T2/FLAIR hyperintensity involving limbic structure. Abnormal CSF as above. EEG epileptiform abnormality/focal slowing
Paraneoplastic cerebellar degeneration (PCD)Severe pan cerebellar ataxia developing in less than 12 weeks, onset appendicularInitial MRI brain usually normal. Later cerebellar atrophy
Chronic gastrointestinal pseudoobstructionSubacute progressive nausea, vomiting, abdominal distention, pain and constipationGI motility study and autonomic reflex screen, thermoregulatory sweat test for associated autonomic dysfunction
Opsoclonus myoclonusInvoluntary chaotic saccades in all directions of gaze, associated with myoclonus and ataxia frequentlyMRI brain usually normal. EMG diagnosis of myoclonus
Chronic gastrointestinal pseudoobstructionSubacute progressive nausea, vomiting, abdominal distention, pain and constipationGI motility study and autonomic reflex screen, thermoregulatory sweat test for associated autonomic dysfunction
Subacute sensory neuronopathyNumbness and pain onset in upper extremity, asymmetric. Progression in less than 12 weeksNerve conduction studies (NCS) - absent or reduced SNAPs, MRI spine enhancing nerve roots. Abnormal CSF as mentioned above.
Lambert-Eaton myasthenic syndrome (LEMS)Proximal weakness with ocular and bulbar involvement. Hypoactive deep tendon reflexes and mild dysautonomia helps clinical differentiation from myasthenia gravisEMG-incremental response on repetitive stimulation


Table 4. Paraneoplastic Antibodies Associated With Cancers and PNS [6, 7]
AntibodyNeoplasm predicted by autoantibodyNeoplasm (%)/frequency of coexisting antibody (%)Clinical features
Nuclear antibodies
  Anti-neuronal nuclear antibody-1 (ANNA-1) (anti-Hu)Small cell lung cancer (SCLC), neuroblastoma, thymoma81/43PEM- limbic, cortical, brainstem encephalitis, PCD, myelitis, PSN, autonomic dysfunction
  ANNA-2 (anti-Ri)Lung cancer, breast cancer86/73Brainstem encephalitis, opsoclonus - myoclonus, PCD
  ANNA-3Lung cancer, upper airway cancer90/30Sensory/sensorimotor neuropathy, cerebellar ataxia, myelopathy, brainstem and limbic encephalopathy
  Anti-glial nuclear antibody (AGNA 1)SCLC90/50LEMS, PCD, sensory neuronopathy, limbic encephalitis, sensory motor neuropathy
  Anti-Ma2Germ cell tumor of testis, lung, GIT, breast, non-Hodgkin’s lymphomaUnknownCerebellar/brainstem syndrome, limbic encephalitis. Narcolepsy like, cataplexy, hypnogogic hallucination
  Zic 4SCLC92/27Limbic encephalitis, cerebellar/brainstem syndrome
Cytoplasmic antibodies
  Purkinje cell cytoplasmic antibody (PCA-1)Ovarian, fallopian, endometrial and breast cancer90/9PCD
  PCA-2SCLC80/63Brainstem/limbic encephalitis, PCD, LEMS, motor neuronopathy
  PCA-TrHodgkin’s lymphoma90/unknownPCD, limbic encephalopathy
  AmphiphysinBreast cancer, lung cancer80/38Stiff-man syndrome, PEM
  CRMP-5 (collapsin response mediated protein)SCLC, thymoma, thyroid, renal cancer80/57PEM, PCD, chorea, optic neuropathy, myelopathy and peripheral neuropathy
  Striational (sarcomeric proteins)SCLC, thymoma, breast cancerUnknownMyasthenia gravis
Cell membrane antibodies
  Voltage gated calcium channel (VGCC) NLung, breast, ovarian cancerUnknownLEMS, cerebellar degeneration
  VGCC P/QSCLCUnknownLEMS, cerebellar degeneration
  AchR, muscleThymoma, SCLCUnknownMyasthenia gravis
  AchR, ganglionicThymoma, SCLCUnknownAutonomic neuropathy
  Voltage gated potassium channel (VGKC) related proteinThymoma, SCLCUnknownLimbic encephalitis, Morvan’s syndrome, PCD, GI dysmotility, parkinsonism, tremor, chorea, sensory motor neuropathy, hyponatremia, dyssomnia and hyperphagia
  NMDA receptorOvarian teratoma59/unknownPsychiatric features and memory loss, orofacial dyskinesia, choreoathetoid movements, abnormal posturing or increased tone, catatonic state and central hypoventilation
  AMPA receptorSCLC, thymoma, breastUnknownLimbic encephalitis, atypical psychosis
  GABA B receptorSCLCUnknownLimbic encephalitis
  Glycine receptorLung cancerUnknownProgressive encephalomyelitis with rigidity and myoclonus (PERM)
  MgluR1Hodgkin’s lymphomaUnknownPCD