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]

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.

References

  1. ↑ Soffer D (1976) Brain tumors simulating purulent meningitis. Eur Neurol 14 (3):192-7. PMID: 1278192
  2. ↑
  3. ↑ 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. ↑ Lee MC, Heaney LM, Jacobson RL, Klassen AC (1975). "Cerebrospinal fluid in cerebral hemorrhage and infarction". Stroke. 6 (6): 638–41. PMID 1198628.
  6. ↑ Birenbaum D, Bancroft LW, Felsberg GJ (2011). "Imaging in acute stroke". West J Emerg Med. 12 (1): 67–76. PMC 3088377. PMID 21694755.
  7. ↑ 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 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 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 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. ↑ 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.

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