Neurosyphilis differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Tarek Nafee, M.D. [2];Mohamadmostafa Jahansouz M.D.[3]

Overview

Differential Diagnosis

Diseases Diagnostic tests Physical Examination Symptoms Past medical history Other Findings
Na+, K+, Ca2+ CT /MRI CSF Findings Gold standard test Neck stiffness Motor or Sensory deficit Papilledema Bulging fontanelle Cranial nerves Headache Fever Altered mental status
Brain tumour[1][2] ✔ Cancer cells[3] MRI ✔ ✔ ✔ ✔ ✔ ✔ Cachexia, gradual progression of symptoms
Delirium tremens ✔ Clinical diagnosis ✔ ✔ ✔ ✔ ✔ ✔ Alcohol intake, sudden witdrawl or reduction in consumption Tachycardia, diaphoresis, hypertension, tremors, mydriasis, positional nystagmus,
Subarachnoid hemorrhage[4] ✔ Xanthochromia[5] CT scan without contrast[6][7] ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔ Trauma/fall Confusion, dizziness, nausea, vomiting
Stroke ✔ Normal CT scan without contrast ✔ ✔ ✔ ✔ ✔ TIAs, hypertension, diabetes mellitus Speech difficulty, gait abnormality
Neurosyphilis[8][9] ✔ ↑ Leukocytes and protein CSF VDRL-specifc

CSF FTA-Ab -sensitive[10]

✔ ✔ ✔ ✔ ✔ ✔ Unprotected sexual intercourse, STIs Blindness, confusion, depression,

Abnormal gait

Viral encephalitis ✔ Increased RBCS or xanthochromia, mononuclear lymphocytosis, high protein content, normal glucose Clinical assesment ✔ ✔ ✔ ✔ ✔ ✔ ✔ Tick bite/mosquito bite/ viral prodome for several days Extreme lethargy, rash hepatosplenomegaly, lymphadenopathy, behavioural changes
Herpes simplex encephalitis ✔ Clinical assesment ✔ ✔ ✔ ✔ ✔ History of hypertension Delirium, cortical blindness, cerebral edema, seizure
Wernicke’s encephalopathy Normal ✔ ✔ ✔ History of alcohal abuse Ophthalmoplegia, confusion
CNS abscess ✔ ↑ leukocytes >100,000/ul, ↓ glucose and ↑ protien, ↑ red blood cells, lactic acid >500mg Contrast enhanced MRI is more sensitive and specific,

Histopathological examination of brain tissue

✔ ✔ ✔ ✔ ✔ ✔ ✔ History of drug abuse, endocarditis, ↓ immune status High grade fever, fatigue,nausea, vomiting
Drug toxicity ✔ ✔ Lithium, Sedatives, phenytoin, carbamazepine
Conversion disorder Diagnosis of exclusion ✔ ✔ ✔ ✔ ✔ Tremors, blindness, difficulty swallowing
Electrolyte disturbance ↓ or ↑ Depends on the cause ✔ ✔ Confusion, seizures
Febrile convulsion Not performed in first simple febrile seizures Clinical diagnosis and EEG ✔ ✔ ✔ ✔ Family history of febrile seizures, viral illness or gastroenteritis Age > 1 month,
Subdural empyema ✔ Clinical assesment and MRI ✔ ✔ ✔ ✔ ✔ ✔ History of relapses and remissions Blurry vision, urinary incontinence, fatigue
Hypoglycemia ↓ or ↑ Serum blood glucose

HbA1c

✔ ✔ ✔ History of diabetes Palpitations, sweating, dizziness, low serum, glucose


Diseases History and Physical Diagnostic tests Other Findings
Motor Deficit Sensory deficit Cranial nerve Involvement Autonomic dysfunction Proximal/Distal/Generalized Ascending/Descending/Systemic Unilateral (UL)

or Bilateral (BL)

or

No Lateralization (NL)

Onset Lab or Imaging Findings Specific test
Adult Botulism + - + + Generalized Descending BL Sudden Toxin test Blood, Wound, or Stool culture Diplopia, Hyporeflexia, Hypotonia, possible respiratory paralysis
Infant Botulism + - + + Generalized Descending BL Sudden Toxin test Blood, Wound, or Stool culture Flaccid paralysis (Floppy baby syndrome), possible respiratory paralysis
Guillian-Barre syndrome[11] + - - - Generalized Ascending BL Insidious CSF: ↑Protein

↓Cells

Clinical & Lumbar Puncture Progressive ascending paralysis following infection, possible respiratory paralysis
Eaton Lambert syndrome[12] + - + + Generalized Systemic BL Intermittent EMG, repetitive nerve stimulation test (RNS) Voltage gated calcium channel (VGCC) antibody Diplopia, ptosis, improves with movement (as the day progresses)
Myasthenia gravis[13] + - + + Generalized Systemic BL Intermittent EMG, Edrophonium test Ach receptor antibody Diplopia, ptosis, worsening with movement (as the day progresses)
Electrolyte disturbance[14] + + - - Generalized Systemic BL Insidious Electrolyte panel ↓Ca++, ↓Mg++, ↓K+ Possible arrhythmia
Organophosphate toxicity[15] + + - + Generalized Ascending BL Sudden Clinical diagnosis: physical exam & history Clinical suspicion confirmed with RBC AchE activity History of exposure to insecticide or living in farming environment. with : Diarrhea, Urination, Miosis, Bradycardia, Lacrimation, Emesis, Salivation, Sweating
Tick paralysis (Dermacentor tick)[16] + - - - Generalized Ascending BL Insidious Clinical diagnosis: physical exam & history - History of outdoor activity in Northeastern United States. The tick is often still latched to the patient at presentation (often in head and neck area)
Tetrodotoxin poisoning[17] + - + + Generalized Systemic BL Sudden Clinical diagnosis: physical exam & dietary history - History of consumption of puffer fish species.
Stroke[18] +/- +/- +/- +/- Generalized Systemic UL Sudden MRI +ve for ischemia or hemorrhage MRI Sudden unilateral motor and sensory deficit in a patient with a history of atherosclerotic risk factors (diabetes, hypertension, smoking) or atrial fibrillation.
Poliomyelitis[19] + + + +/- Proximal > Distal Systemic BL or UL Sudden PCR of CSF Asymmetric paralysis following a flu-like syndrome.
Transverse myelitis[20] + + + + Proximal > Distal Systemic BL or UL Sudden MRI & Lumbar puncture MRI History of chronic viral or autoimmune disease (e.g. HIV)
Neurosyphilis[8][9] + + - +/- Generalized Systemic BL Insidious MRI & Lumbar puncture CSF VDRL-specifc

CSF FTA-Ab -sensitive[10]

History of unprotected sex or multiple sexual partners.

History of genital ulcer (chancre), diffuse maculopapular rash.

Muscular dystrophy[21] + - - - Proximal > Distal Systemic BL Insidious Genetic testing Muscle biopsy Progressive proximal lower limb weakness with calf pseudohypertrophy in early childhood. Gower sign positive.
Multiple sclerosis exacerbation[22] + + + + Generalized Systemic NL Sudden ↑CSF IgG levels

(monoclonal)

Clinical assessment and MRI [23] Blurry vision, urinary incontinence, fatigue
Amyotrophic lateral sclerosis[24] + - - - Generalized Systemic BL Insidious Normal LP (to rule out DDx) MRI & LP Patient initially presents with upper motor neuron deficit (spasticity) followed by lower motor neuron deficit (flaccidity).
Inflammatory myopathy[25] + - - - Proximal > Distal Systemic UL or BL Insidious Elevated CK & Aldolase Muscle biopsy Progressive proximal muscle weakness in 3rd to 5th decade of life. With or without skin manifestations.

Neurosyphilis must be differentiated from other causes of headache,seizures and loss of consciousness.

Diseases Symptoms Physical Examination Past medical history Diagnostic tests Other Findings
Headache ↓LOC Motor weakness Abnormal sensory Motor Deficit Sensory deficit Speech difficulty Gait abnormality Cranial nerves CT /MRI CSF Findings Gold standard test
Meningitis + - - - - + + - - History of fever and malaise - ↑ Leukocytes,

↑ Protein

↓ Glucose

CSF analysis[26] Fever, neck

rigidity

Encephalitis + + +/- +/- - - + +/- + History of fever and malaise + ↑ Leukocytes, ↓ Glucose CSF PCR Fever, seizures, focal neurologic abnormalities
Brain tumor[27] + - - - + + + - + Weight loss, fatigue + Cancer cells[3] MRI Cachexia, gradual progression of symptoms
Hemorrhagic stroke + + + + + + + + - Hypertension + - CT scan without contrast[6][7] Neck stiffness
Subdural hemorrhage + + + + + - - - + Trauma, fall + Xanthochromia[5] CT scan without contrast[6][7] Confusion, dizziness, nausea, vomiting
Neurosyphilis[8][9] + - + + + + - + - STIs + ↑ Leukocytes and protein CSF VDRL-specifc

CSF FTA-Ab -sensitive[10]

Blindness, confusion, depression,

Abnormal gait

Complex or atypical migraine + - + + - - + - - Family history of migraine - - Clinical assesment Presence of aura, nausea, vomiting
Hypertensive encephalopathy + + - - - - + + - Hypertension + - Clinical assesment Delirium, cortical blindness, cerebral edema, seizure
Wernicke’s encephalopathy - + - - - + + + + History of alcohal abuse - - Clinical assesment and lab findings Ophthalmoplegia, confusion
CNS abscess + + - - + + + - - History of drug abuse, endocarditis, immunosupression + ↑ leukocytes, ↓ glucose and ↑ protien MRI is more sensitive and specific High grade fever, fatigue,nausea, vomiting
Drug toxicity - + - + + + - + - - - - Drug screen test Lithium, Sedatives, phenytoin, carbamazepine
Conversion disorder + + + + + + + + History of emotional stress - - Diagnosis of exclusion Tremors, blindness, difficulty swallowing
Metabolic disturbances (electrolyte imbalance, hypoglycemia) - + + + + + - - + - - Hypoglycemia, hypo and hypernatremia, hypo and hyperkalemia Depends on the cause Confusion, seizure, palpitations, sweating, dizziness, hypoglycemia
Multiple sclerosis exacerbation - - + + - + + + + History of relapses and remissions + ↑ CSF IgG levels

(monoclonal bands)

Clinical assesment and MRI [23] Blurry vision, urinary incontinence, fatigue
Seizure + + - - + + - - + Previous history of seizures - Mass lesion Clinical assesment and EEG [28] Confusion, apathy, irritability,


References

  1. ↑ Soffer D (1976) Brain tumors simulating purulent meningitis. Eur Neurol 14 (3):192-7. PMID: 1278192
  2. ↑
  3. ↑ 3.0 3.1 Weston CL, Glantz MJ, Connor JR (2011). "Detection of cancer cells in the cerebrospinal fluid: current methods and future directions". Fluids Barriers CNS. 8 (1): 14. doi:10.1186/2045-8118-8-14. PMC 3059292. PMID 21371327.
  4. ↑ Yeh ST, Lee WJ, Lin HJ, Chen CY, Te AL, Lin HJ (2003) Nonaneurysmal subarachnoid hemorrhage secondary to tuberculous meningitis: report of two cases. J Emerg Med 25 (3):265-70. PMID: 14585453
  5. ↑ 5.0 5.1 Lee MC, Heaney LM, Jacobson RL, Klassen AC (1975). "Cerebrospinal fluid in cerebral hemorrhage and infarction". Stroke. 6 (6): 638–41. PMID 1198628.
  6. ↑ 6.0 6.1 6.2 Birenbaum D, Bancroft LW, Felsberg GJ (2011). "Imaging in acute stroke". West J Emerg Med. 12 (1): 67–76. PMC 3088377. PMID 21694755.
  7. ↑ 7.0 7.1 7.2 DeLaPaz RL, Wippold FJ, Cornelius RS, Amin-Hanjani S, Angtuaco EJ, Broderick DF; et al. (2011). "ACR Appropriateness Criteria® on cerebrovascular disease". J Am Coll Radiol. 8 (8): 532–8. doi:10.1016/j.jacr.2011.05.010. PMID 21807345.
  8. ↑ 8.0 8.1 8.2 Liu LL, Zheng WH, Tong ML, Liu GL, Zhang HL, Fu ZG; et al. (2012). "Ischemic stroke as a primary symptom of neurosyphilis among HIV-negative emergency patients". J Neurol Sci. 317 (1–2): 35–9. doi:10.1016/j.jns.2012.03.003. PMID 22482824.
  9. ↑ 9.0 9.1 9.2 Berger JR, Dean D (2014). "Neurosyphilis". Handb Clin Neurol. 121: 1461–72. doi:10.1016/B978-0-7020-4088-7.00098-5. PMID 24365430.
  10. ↑ 10.0 10.1 10.2 Ho EL, Marra CM (2012). "Treponemal tests for neurosyphilis--less accurate than what we thought?". Sex Transm Dis. 39 (4): 298–9. doi:10.1097/OLQ.0b013e31824ee574. PMC 3746559. PMID 22421697.
  11. ↑ Talukder RK, Sutradhar SR, Rahman KM, Uddin MJ, Akhter H (2011). "Guillian-Barre syndrome". Mymensingh Med J. 20 (4): 748–56. PMID 22081202.
  12. ↑ Merino-Ramírez MÁ, Bolton CF (2016). "Review of the Diagnostic Challenges of Lambert-Eaton Syndrome Revealed Through Three Case Reports". Can J Neurol Sci. 43 (5): 635–47. doi:10.1017/cjn.2016.268. PMID 27412406.
  13. ↑ Gilhus NE (2016). "Myasthenia Gravis". N Engl J Med. 375 (26): 2570–2581. doi:10.1056/NEJMra1602678. PMID 28029925.
  14. ↑ Ozono K (2016). "[Diagnostic criteria for vitamin D-deficient rickets and hypocalcemia-]". Clin Calcium. 26 (2): 215–22. doi:CliCa1602215222 Check |doi= value (help). PMID 26813501.
  15. ↑ Kamanyire R, Karalliedde L (2004). "Organophosphate toxicity and occupational exposure". Occup Med (Lond). 54 (2): 69–75. PMID 15020723.
  16. ↑ Pecina CA (2012). "Tick paralysis". Semin Neurol. 32 (5): 531–2. doi:10.1055/s-0033-1334474. PMID 23677663.
  17. ↑ Bane V, Lehane M, Dikshit M, O'Riordan A, Furey A (2014). "Tetrodotoxin: chemistry, toxicity, source, distribution and detection". Toxins (Basel). 6 (2): 693–755. doi:10.3390/toxins6020693. PMC 3942760. PMID 24566728.
  18. ↑ Kuntzer T, Hirt L, Bogousslavsky J (1996). "[Neuromuscular involvement and cerebrovascular accidents]". Rev Med Suisse Romande. 116 (8): 605–9. PMID 8848683.
  19. ↑ Laffont I, Julia M, Tiffreau V, Yelnik A, Herisson C, Pelissier J (2010). "Aging and sequelae of poliomyelitis". Ann Phys Rehabil Med. 53 (1): 24–33. doi:10.1016/j.rehab.2009.10.002. PMID 19944665.
  20. ↑ West TW (2013). "Transverse myelitis--a review of the presentation, diagnosis, and initial management". Discov Med. 16 (88): 167–77. PMID 24099672.
  21. ↑ Falzarano MS, Scotton C, Passarelli C, Ferlini A (2015). "Duchenne Muscular Dystrophy: From Diagnosis to Therapy". Molecules. 20 (10): 18168–84. doi:10.3390/molecules201018168. PMID 26457695.
  22. ↑ Filippi M, Preziosa P, Rocca MA (2016). "Multiple sclerosis". Handb Clin Neurol. 135: 399–423. doi:10.1016/B978-0-444-53485-9.00020-9. PMID 27432676.
  23. ↑ 23.0 23.1 Giang DW, Grow VM, Mooney C, Mushlin AI, Goodman AD, Mattson DH; et al. (1994). "Clinical diagnosis of multiple sclerosis. The impact of magnetic resonance imaging and ancillary testing. Rochester-Toronto Magnetic Resonance Study Group". Arch Neurol. 51 (1): 61–6. PMID 8274111.
  24. ↑ Riva N, Agosta F, Lunetta C, Filippi M, Quattrini A (2016). "Recent advances in amyotrophic lateral sclerosis". J Neurol. 263 (6): 1241–54. doi:10.1007/s00415-016-8091-6. PMC 4893385. PMID 27025851.
  25. ↑ Michelle EH, Mammen AL (2015). "Myositis Mimics". Curr Rheumatol Rep. 17 (10): 63. doi:10.1007/s11926-015-0541-0. PMID 26290112.
  26. ↑ Carbonnelle E (2009). "[Laboratory diagnosis of bacterial meningitis: usefulness of various tests for the determination of the etiological agent]". Med Mal Infect. 39 (7–8): 581–605. doi:10.1016/j.medmal.2009.02.017. PMID 19398286.
  27. ↑ Morgenstern LB, Frankowski RF (1999). "Brain tumor masquerading as stroke". J Neurooncol. 44 (1): 47–52. PMID 10582668.
  28. ↑ Manford M (2001). "Assessment and investigation of possible epileptic seizures". J Neurol Neurosurg Psychiatry. 70 Suppl 2: II3–8. PMC 1765557. PMID 11385043.

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