A CRAWLING

SUSPICION… SHIO YEN TIO

WESTERN HEALTH

Mrs AA • 31 year-old Sudanese lady

• No past medical history, no regular medications

• 4/12 history of progressive weakness of lower limbs

• Needing crutches for mobilisation

• Neuropathic pain

• Impaired sensation from hip down

• 7kg weight loss

• No back pain

• Normal cranial nerves, upper limbs, bladder and bowel functions

Mrs AA

• Came to Melbourne from South Sudan in 2004

• Cleaner at school

• No recreational/ intravenous drug/ alcohol use, non smoker

• 2 previous partners – no history of STIs

• No precipitating event she could recall

Physical Examination • Walking with an aid of 2 crutches, slow ataxic gait

• Normal upper limb neurological and cranial nerves examination

Right Left

Tone Normal, no wasting Normal, no wasting

Power

Hip flex/ ext

Hip abd/ add

Knee flex/ ext

Ankle flex/ ext

Ankle inv/ eversion

3+/5

3+/5

3+/5

4/5

4/5

3-/5

3-/5

3-/5

3+/5

3+/5

Reflexes

Knee

Ankle

Plantar

Absent

Absent

Downgoing

Absent

Absent

Downgoing

Coordination Can’t be tested Can’t be tested

Sensation

Joint position

Pinprick

Vibration

Normal

Impaired to knee

Impaired to knee

Normal

Impaired to hip

Impaired to iliac crest

CSF Opening

pressure

WCC Protein

(0.15 – 0.45)

Glucose

(2.0-3.9)

17/12/14 11cm H20 300 (all

mononuclear)

2.46 2.1

19/12/14 Not done 200 (all

mononuclear)

1.48 2.3

Investigations

• Possible oligoclonal IgG band detected (but no serum to compare with)

• TB PCR/ AFB smear and culture negative

• Cryptococcal antigen negative

• Viral PCR negative – CMV, EBV, enterovirus, VZV, HSV 1 and HSV 2

• Flow cytometry negative

• cytology: mild lymphocytosis, no eosinophils

• CSF ACE level <12

Investigations

Negative tests:

• Vasculitic screen

• B12 level

• SPEP

• Serum free light chain

• Urine BJP

• HIV

• Hepatitis B

• Hepatitis C

• HTLV

• Syphilis serology

• Quantiferon gold

Investigation

• CT C/A/P: no evidence of neoplastic process

• MRI whole spine: diffuse and marked thickening and enhancing of nerve roots

extending from the conus through to cauda equina

• MRI brain: no enhancement, essentially normal

• Nerve conduction study: normal, no demyelination

Progress

• Transferred to RMH for dural, arachnoid and nerve root biopsy

Intra-op finding: swollen cauda equina nerve roots

Dura histology: NAD

Arachnoid: mature T lymphocytes, eosinophils and macrophages, no atypia

Nerve roots: perineural inflammatory infiltrates

No necrotising granulomatous inflammation and tumour

Progress

• Received 3 doses of IV methylprednisolone

• HRZE + dexamethasone started on 12/1/15

Visual disturbance – ethambutol ceased 28/1/15

Steroids induced diabetes started on insulin

Abnormal LFTs improved over time

Progress • Overall slow improvement

• Dexamethasone prednisolone, and Bactrim for PJP prophylaxis

• Schistosoma serology 13.5 (<8.5), strongyloides serology negative

3 x urine and 2 x faecal samples negative for Schistosome ova

Schistosoma serology on CSF (Westmead, unvalidated) – negative

POSSIBLE NEUROSCHISTOSOMIASIS

(SCHISTOSOMAL MYELORADICULOPATHY)

Progress • Praziquantel 40mg/ kg given as a single dose on 18/3/15

Vomited 2nd course given

Increasing early morning headache

Admitted over Easter for meningitis work up:

Raised opening pressure 30cm H20

CSF: WCC 700 (mostly mononuclear), protein 1.47, glucose 3.7

Prednisolone doubled in dose

Headache improved

Outpatient Review (May/ July)

• Marked improvement in lower limbs weakness

• Neuropathic pain resolved

• Ongoing paraesthesia of dorsum of feet

• TB treatment downgraded to Isoniazid and Rifampicin – aim 12-18 months

of treatment

Summary

• 31 year-old lady

• 4/12 history of bilateral lower limbs weakness, paraesthesia and neuropathic pain.

• CSF with high lymphocyte counts and protein

• MRI showed thickened nerve roots with enhancement from conus to cauda equina.

• Nerve roots biopsy – clusters of T lymphocytes, eosinophils and macrophages

• Possible schistosomal myeloradiculopathy

• Neurotuberculosis/ spinal tuberculosis has not been excluded

Neuroschistosomiasis (Schistosomal myeloradiculopathy)

• Introduction & epidemiology

• Pathogenesis

• Clinical features

• Investigations

• Treatment & prognosis

Epidemiology

• World Health Organization (WHO) data 1:

schistosomiasis occurs in 78 countries

100 million with some clinical manifestation

20 million with severe forms of disease

261 million people required preventive treatment in 2013

40 million people were treated for schistosomiasis in 2013

• Annually, over 200,000 people die as a consequence of schistosomiasis. 2

• Schistosomiasis is a Neglected Tropical Disease (NTD). 3

Gryseels et al.

South Sudan, where

Mrs AA is from.

Neuroschistosomiasis

• Neuroschistosomiasis, when symptomatic, is a severe disorder in which prognosis depends

largely on early treatment.

• Not uncommon, under-recognised and morbidity seriously under-estimated. 6

In 1948, Faust published a review on the 82 cases of ectopic schistosomiasis.

8/82 patients presented with signs of spinal cord lesions.

3 of these patients were infected with Schistosoma mansoni.

Conclusion: Be aware of this!!

The American Journal of Tropical Medicine and Hygiene,

28: 175-199, 1948

Author Journal Title Comment

Scrimgeor &

Gajdusek et

al

Brain 1985 Involvement of The Central

Nervous System in

Schistosoma mansoni and S.

haematobium Infection A

Review

Probably contributed to

1% of all non-traumatic

paraplegia in Tanzania,

presumed cause in 5% of

other cases

Carod Artal

et al

Neurology

2004

Schistosoma mansoni

myelopathy

Prevalence:

approximately 5.6%

amongst patients with

inflammatory

myelopathies, Brazil

Spinal Cord Schistosomiasis, 2013, Freitas et al.

The Lancet, 2013, Volume 381 , Issue 9879 , 1788

Spinal Cord Schistosomiasis, 2013, Freitas et al.

Pathogenesis

http://www.yourgenome.org

Neurosciencejournal.org

Pathogenesis

• The host’s cellular inflammatory response to eggs

• Host’s inflammatory response varies in intensity: negligible clinical signs to severe

reaction resulting in space-occupying granulomatous mass and nervous tissue

necrosis

• ?autoimmune process vasculitis and ischemia

Pathogenesis

Clinical Features

NEUROSCHISTOSOMIASIS

Encephalitic or Cerebral

Schistosomiasis/

CNS Pseudotumoral

Schistosomiasis 13, 14

• Encephalopathy with headache

• Nystagmus/ visual impairment

• Delirium & seizures

• Motor deficits

• Ataxia

• Speech disturbances

• Cranial nerves abnormalities

Spinal Cord Schistosomiasis 14

1. Acute transverse myelitis

2. Subacute progressive

myeloradiculopathy

• Lumbar and/or lower limb pain

• Weakness of the lower limbs

• Anaesthesia/hypoesthesia of the lower

limbs

• Paraparesis of the lower limbs

• Bladder dysfunction

• Intestinal dysfunction

• Erectile dysfunction

Diagnosis/ Investigations • Difficult!

Cerebral and spinal schistosomiasis. Carod Artal FJ, 2012

• Spinal cord schistosomiasis (presumptive diagnosis) 15, 16:

a) Typical clinical manifestations (medullar and/ or radicular symptoms) and signs

resulting from lesions of spinal cord

b) Proof of exposure to Schistosoma through parasitological and/ or immunological

methods

c) Exclusion of other possible causes of myelopathy

Spinal Cord Schistosomiasis, Freitas et al, 2013

Diagnosis/ Investigations

Spinal cord MRI at T2

sequence, showing

swelling of conus

medullaris.

Neuroschistosomiasis, Francisco

Javier, Carod-Artal

Expert Rev. Anti Infect. Ther. 8(11),

1307–1318 (2010)

CARVALHO, Gustavo Balthazar da Silveira et al. 2013

1. Medullary schistosomiasis – conus medullaris expansion, linear and nodular

enhancement pattern

2. Tuberculosis – intramedullary tuberculoma is rare (2% of neurotuberculosis

cases); defined granuloma which is hypersignal in T2, peripheral annular

enhancement

3. Neurosarcoidosis – multiple and centrally located, heterogeneously contrast-

enhanced lesions observed with hypersignal on T2 images

4. Neurocysticercosis – intramedullary involvement is rare (2-5%). T2 images

showing multiple hypersignal cyst like nodules

5. Viral transverse myelitis – most frequently affecting thoracic segments and less

frequently conus medullaris. Centrally located hypersignal on T2, with or without

post contrast enhancement, thickening of spinal cord

Radiol Bras, 2013, vol.46, n.1 pp. 51-55

Spinal Tuberculosis

Neurosarcordosis

Neurocysticercosis

Herpes- related myelitis

Sagittal (A) and coronal (B) T2-

weighted MRI of the brain - confluent

high signal in the cerebellum,

especially in the right hemisphere

Coronal

gadolinium-enhanced

T1-weighted

sequence shows

areas of nodular

enhancement in the

cerebellum,

especially in the right

hemisphere.

Neuroschistosomiasis: clinical symptoms and pathogenesis

Ferrari, Teresa Cristina A et al.

The Lancet Neurology, Volume 10, Issue 9, 853 - 864

• Urine, stool (Kato-Katz technique) and rectal mucosa examination for schistosoma ova

Can be detected in 40% of patient with neuroschistosomiasis 12, 16

• CSF 15, 16

protein in 95% of cases

leukocytes (predominantly lymphocytes) in 98% of cases

Presence of eosinophils in 40.8% of cases

in gamma globulin levels in 76% of cases

• Serology in serum and CSF

detect antibodies against schistosome crude egg and soluble worm antigens

ELISA, haemagglutination and/or indirect immunofluorescence

ELISA can be positive in CSF, but required further validation 21

• Urine-based PCR assay has been developed for the detection of S. mansoni DNA in

human urine samples - sensitivity of 100 %, specificity of 91.2 % in endemic areas 22

Investigations

• Definitive diagnosis :

Biopsy - may show schistosome ova in various stages of evolution, surrounding

inflammatory reaction

The granuloma around the ova have a necrotic centre that contains schistosome

egg and/or an egg cluster surrounded by epithelioid cells, giant cells and

lymphocytes, and an outer layer of eosinophils, fibroblasts and plasma cells

Freitas et al, 2013 Carod Artal et al, 2012

Diagnosis/ Investigations

• Combination of praziquantel and corticosteroids

• No established guidelines on duration

• 16 patients with schistosomal myeloradiculopathy

• Treated with oral praziquantel (50 mg/kg in a single dose) and

methylprednisolone (15 mg/kg/day intravenously for 5 days) followed by

prednisone (1 mg/kg/day orally for 6 months)

• Prospective evaluation of clinical outcome in 2nd and 6th month of treatment,

including changes in MRI spine

Clinical Infectious Diseases 2004 39: 1618-1624

• Statistically significant improvement observed in both the 2nd and 6th months

of corticosteroid therapy

• 12 /16 patients had repeat MRI – 3 showed normalisation, 9 showed

improvement in changes

• But this did not necessarily correlate with clinical improvement

• Time to treatment is important – within 30 days

• Steroids > 2 months is associated with better clinical outcome

Conclusion • Neuroschistosomiasis is a severe disorder, often under-recognised.

• Huge migrant population in Victoria.

• Maintain awareness.

• Early diagnosis is essential to reduce severity and disability resulting from it.

• Development and validation of new ELISA and other diagnostic techniques is needed.

• Currently no consensus on duration of schistosomicidal drugs and steroid therapy –

further clinical trials needed.

Thank you!!

• Western Health ID Team

• Western Health Neurology Team

• RMH Neurosurgical Team

• Dorevitch/ Microbiology Department Western Health

• Westmead ICPMR

References

1. http://www.who.int/mediacentre/factsheets/fs115/en/

2. World Health Organization (WHO) http://www.who.int/mediacentre/factsheets/fs115/en/index.html (accessed 7 September 2012)

3. https://www.iamat.org/risks/schistosomiasis

4. Gryseels B, Polman K, Clerinx J et al (2006) Human schistosomiasis. Lancet 368:1106–1118

5. http://www.cdc.gov/parasites/schistosomiasis/biology.html

6. Drummond SC, Silva LC, Amaral RS, Sousa-Pereira SR, Antunes CM, Lambertucci JR. Morbidity of schistosomiasis mansoni in

the state of Minas Gerais, Brazil. Memórias do Instituto Oswaldo Cruz 101: 37-44, 2006.

7. http://www.intechopen.com/books/parasitic-diseases-schistosomiasis/spinal-cord-schistosomiasis

8. Faust EC. An inquiry into the ectopic lesions in schistosomiasis. The American Jounral of Tropical Medicine and Hygiene 28:

175-199, 1948

9. Scrimgeour EM, Gajdusek DC. Involvement of the central nervous system in Schistosoma mansoni and Schistosoma

haematobium infection: a review. Brain 108: 1023-1038, 1985.

10. Carod-Artal FJ, Vargas AP, Horan TA, Marinho PB, Coelho-Costa PH. Schistosoma mansoni myelopathy: clinical and pathologic

findings. Neurology 63: 388-391, 2004.

11. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)60317-7/fulltext?rss%3Dyes

12. Cerebral and Spinal Schistosomiasis, Current Neurology and Neuroscience Reports, December 2012, Volume 12, Issue 6, pp

666-674

13. Ross AG, McManus DP, Farrar J, et al. Neuroschistosomiasis. J Neurol 2012; 259:22.

14. Neuroschistosomiasis, November 2010, Vol. 8, No. 11 , Pages 1307-1318 (doi:10.1586/eri.10.111), Francisco Javier Carod-Artal

15. http://www.intechopen.com/books/parasitic-diseases-schistosomiasis/spinal-cord-schistosomiasis

16. Guidelines for the diagnosis and treatment of schistosomal myeloradiculopathy, Lambertucci JR1, Silva LC, do Amaral RS, Rev

Soc Bras Med Trop. 2007 Sep-Oct;40(5):574-81.

17. Neuroschistosomiasis, Francisco Javier, Carod-Artal, Expert Rev. Anti Infect. Ther. 8(11), 1307–1318 (2010)

18. CARVALHO, Gustavo Balthazar da Silveira et al. Magnetic resonance imaging in the differential diagnosis of infectious and

inflammatory conus medullaris lesions. Radiol Bras [online]. 2013, vol.46, n.1 [cited 2015-07-18], pp. 51-55

19. Neuroschistosomiasis: clinical symptoms and pathogenesis, Ferrari, Teresa Cristina A et al. The Lancet Neurology , Volume 10 ,

Issue 9 , 853 - 864

20. • Zhu H, Yu C, Xia X, et al. Assessing the diagnostic accuracy of immunodiagnostic techniques in the diagnosis of

schistosomiasis japonica: a meta-analysis. Parasitol Res. 2010;5:1067–73. A meta-analysis about the accuracy of

immunodiagnostic techniques in schistosomiasis japonica.

21. Ferrari TC. A laboratory test for the diagnosis of neuroschistosomiasis. Neurol Res. 2010;32:252–62.

22. Enk MJ, Oliveira E, Silva G, Rodrigues NB. Diagnostic accuracy and applicability of a PCR system for the detection of

Schistosoma mansoni DNA in human urine samples froman endemic area. PLoS One. 2012;7:e38947.

23. FREITAS, André Ricardo Ribas; OLIVEIRA, Augusto César Penalva and SILVA, Luiz Jacintho. Schistosomal myeloradiculopathy

in a low-prevalence area: 27 cases (14 autochthonous) in Campinas, São Paulo, Brazil. Mem. Inst. Oswaldo Cruz [online]. 2010,

vol.105, n.4 [cited 2015-07-18], pp. 398-408

24. Luciana C. S. Silva, Pedro E. Maciel, João G. R. Ribas, Sílvio R. Souza-Pereira, Carlos M. Antunes, and José R. Lambertucci

Treatment of Schistosomal Myeloradiculopathy with Praziquantel and Corticosteroids and Evaluation by Magnetic Resonance

Imaging: A Longitudinal Study. Clinical Infectious Diseases 2004 39: 1618-1624.

25. CARVALHO, Gustavo Balthazar da Silveira et al. Magnetic resonance imaging in the differential diagnosis of infectious and

inflammatory conus medullaris lesions. Radiol Bras [online]. 2013, vol.46, n.1 [cited 2015-07-19], pp. 51-55 .