Clinical meet

Dr.H.B.Prasad Unit

A case of PLHIV with Paraplegia

Dr.Ajitkumar K.Jadhav JR (II)

Date :- 2nd April , 2011

HISTORY42 yr , male , Labourer , r/o Pune .

K/c/o PLHIV since last 1 ½ yrs on ART (ZL+ Efa )

CD4- 120/cmm

Chief complaints • Inability to walk - 2 months

weakness started in both lower limbs, associated with looseness , progressed to bed ridden state in last 15 days

• Fever - on and off since 1 month

moderate grade , associated with night sweats , relieved with antipyretics

• Easy fatigability and exertional dyspnoea – 1month

H/o Pulmonary Kochs 6 months back ,was still on AKT

No h/o• trauma to back• Similar episode in the past

Decreased sensations below the level of umbilicus

No bowel/bladder complaints

Examination

General Examination:

Avg. built ,poorly nourished

Ht -157 cm ,Wt – 40 kg ,BMI - 17

Conscious ,oriented

Febrile

Pulse - 102/min

BP - 110/70 mmHg

Pallor ++

Multiple matted lymph nodes in Cervical region ,1 cm in size

No oedema /icterus / cyanosis /clubbing

Systemic Examination :CVS – S1S2 heard well, Tachycardia RS – Breath sounds were decreased in Rt. IAA with stony

dull purcussion note ,with no adventious sounds Rest lung fields were clear

P/A –Soft , Liver -palpable 3 cm , firm Spleen - Palpable 5 cm , firm

No free fluid CNS –

Higher functions and Cranial nerves were normal Motor system

Nutrition – mild wasting was present Tone –Normal in both Upper Limbs and

decreased in both Lower Limbs

Power - Grade V in both upper limbs Grade II in both lower limbs

Co-ordination – Normal in upper limbs Could not be tested in lower limbs

Reflexes – DTR ++ in both upper limbs +++ in both lower limbs

Superficial- lower abdominals were absent Plantars were both extensors

Sensory system

Pain , Temp,Touch Joint position & Vibration Spine showed gibbus at the level of T-8 vertebra ,

Which was tender

decreased below the level Umbilicus around T 12

• Young male PLHIV on ART , with pulm kochs on AKT with anemia (likely AZT induced ) with chronic progressive paraplegia , with sensory involvement ,without bowel / bladder involvement and with lymphadenopathy and hepato-splenomegaly

Differentials?

Compressive myelopathy involving thoracic spine likely

• Potts spine • TB myelitis• Disseminated hematological malignancy like

Lymphoma • bacterial spinal abscess

Investigations Hb- 3.7 gm %MCV – 112 fl TLC – 9700/ cmm DLC – P67 L26 E03 M04 B0 mild anisocytosis,normocytes 2 +, microcytes 1 + ,few

macrocytes ,polychromasia 2 +, moderate hypochromiaPlatelet count - 2.48 lac Retic count -8 %ESR- 57 mm at the end of 1 hrSr. Creatinine 1.7 mg %Total bilirubin – 2.5 mg % , Direct 1.6 mg%SGOT/SGPT – 45/39 (IU/L)Total proteins – 5.4 gm %

Chest Xray

-Right sided loculated Pleural effusion with

Underlying lung collapse pleural thickening

USG abdomen • Hepatosplenomegaly with mild ascitis • Rt psoas abscess with echogenic mesentry • B/L enlarged echogenic kidneys

X ray Thoraco-lumbar spine

Showing compression collapse of D9-D10 vertebrae with anterior wedging in lateral film

MR Scan of dorsal spine reveals :- • Altered marrow signals appearing hypointense on T1 and hyperintense on STIR images are noted in D6 , D7 to D8 & 9 vertrbral bodies and posterior neural arches of D9 & D10 vertebrae. s/o infiltration and inflammation in vertebral bodies •Pre and bilateral paravertebral T2 hyperintense soft tissue component extending from D3 to D11 vertebral bodies ( abscesses ) with anterior epidural soft tissue seen from D9 to D10 •Swollen cord with T2 hyperintense signals longitudinally along D8/10 vertebra suggestive of cord edema / infective myelitis.• Loculated thick walled right pleural effusion –? empyema.

• Altered marrow signals appearing hypointense on T1 and hyperintense on STIR images are noted in D6 , D7 to D8 & 9 vertrbral bodies and posterior neural arches of D9 & D10 vertebrae. s/o infiltration and inflammation in vertebral bodies •Pre and bilateral paravertebral T2 hyperintense soft tissue component extending from D3 to D11 vertebral bodies ( abscesses ) with anterior epidural soft tissue seen from D9 to D10 •Swollen cord with T2 hyperintense signals longitudinally along D8/10 vertebra suggestive of cord edema / infective myelitis.• Loculated thick walled right pleural effusion –? empyema.

In view of reduction of intermediate disc spaces , associated pre & para spinal abscesses, possibility of multicentric tuberculosis is more likely, needs histopathological corelation

In view of reduction of intermediate disc spaces , associated pre & para spinal abscesses, possibility of multicentric tuberculosis is more likely, needs histopathological corelation

Patient was continued on - ART (LS + Efa ) - AKT with addition of steroids,hematinics .

The question that remained unanswered was why did patient develop paraplegia despite being on AKT

???

Meanwhile we received a PBS report from pathology dept stating thatRBC : mild anisocytosis , microcytes 1 + ,few macrocytes

polychromasia 2 +, moderate hypochromia TLC : 60000 /cmmDLC : • Neutrophils :- 35 % • Monocytes :- 5 % • Lymphocytes – 5 % • Abnormal cells – 55% abnormal cells are large cells with High N:C

ratio , folded nucleus and scanty , bluish cytoplasm. Few cells show prominent nucleoli. Suggestive of Lymphoid cells

• Platelet : appear scattered and reduced. • Parasites : Not seen in present smearAdvice : Follow up with bone marrow aspiration. Special stain report follows.

BM Aspiration

Hypercellular marrow with diffuse infiltration by large lymphoid cells of heterogenous morphology

• Erythroid series : Megaloblastic erythropoiesis • Granulocyte series : relatively depressed • Myeloid / Erythroid ratio : 9:1

Differential counts :

Blast like cells - 70 % Basophils -00 %

Promyelocytes – 01% Eosinophils -01%

Myelocytes - 03% Lymphocytes- 04%

Metamyelocytes -02% nRBC : 10%

Band cells – 03% Plasma cells -03%

IMPRESSION :

High grade Non –Hodgkin’s Lymphoma (? Burkitt’s Lymphoma )High grade Non –Hodgkin’s Lymphoma (? Burkitt’s Lymphoma )

Final Diagnosis

Patient of PLHIV with Pulmonary Koch’s(On ART and AKT ) with High grade NHL (? Burkitt’s Lymphoma ) with AZT induced anemia with compressive myelopathy most likely due to TB and Lymphoma

• As patient was critically ill ,and non affording , immunophenotyping and cytogenetics studies was not possible

• As a desperate measure we started him on chemotherapy ---Cyclophosphamide , Vincristin , Adriamycin and Prednisolone , as per Hemato -oncologist ‘s opinion

• During the course of treatment pt developed altered sensorium, for that Lumbar puncture was tried but no fluid could be tapped .

• Unfortunately we lost the pt during the course of illness

(Day 2 of chemotherapy)

Discussion

Spinal cord involvement in HIV patients

• Myelopathy is seen ~20% of patients with AIDS, often as part of HIV encephalopathy• CMV infection causes Progressive Lumbosacral Polyradiculopathy • HTLV-I-associated myelopathy (HAM) -Tropical spastic paraparesis• Neurosyphilis (Meningeal, Meningovascular , General paresis ,

Tabes dorsalis ) • Infection with herpes simplex or varicella-zoster , EBV (Rapidly progressive symmetric lower limbs weakness)• TB • Lymphoma

Lymphomas in HIV • Lymphoma is a late manifestation of HIV infection, generally

occurring in patients with CD4+ T cell counts <200/ uL• 90% are B cell in phenotype, and • half contain EBV DNA Three main categories • Grade III or IV immunoblastic lymphoma :-

• 60 % of all lymphomas ,• associated with pleural, pericardial, and/or peritoneal

effusions in the absence of discrete nodal or extranodal masses,

• HHV-8 DNA sequences have been found • Burkitt's lymphoma :- 20% cases , Small noncleaved cell lymphoma • Primary CNS lymphoma. :-

• Mostly positive for EBV , • generally presents with focal neurologic deficits, including

cranial nerve findings, headaches, and/or seizures.

Burkitt’s lymphoma • 30%–40% of non-Hodgkin’s lymphoma in HIV+ patients • Burkitt’s lymphoma was estimated to be 1,000 times more common in

HIV+ individuals than in the general population  

• The diagnosis of Burkitt’s lymphoma in an HIV+ individual often represents the first AIDS-defining criterion.

• HIV is involved in lymphomagenesis  via • cytokine deregulation• chronic antigenic stimulation• decreased immune surveillance

Lymphoma often involves lymph nodes, bone marrow, and extranodal sites, most often in the abdomen , liver ,CNS and lungs

Burkitt,s lymphoma in HIV is very aggressive tumour with poor response to chemotherapy , difficult to achieve complete remission , and less proven response to Rituximab .  

Multicentric Castleman's disease –

This is an HHV-8 associated lymphoproliferative disorder , usually associated with generalized lymphadenopathy, hepatosplenomegaly, and systemic symptoms of fever, fatigue, and weight loss.

Treatment recommendations: Systemic non-Hodgkin’s lymphoma• All patients with CD4 <100/mm3: Low-dose chemotherapy• CD4 >100/mm3: Consider standard-dose chemotherapy in selected patients.• Antibiotic prophylaxis for P. carinii in all patients.• Meningeal prophylaxis for those with small noncleaved histology, bone

marrow involvement, paranasal sinus involvement, or epidural disease.Antiviral therapy:• Combination antiviral therapy should be continued with chemotherapy• Zidovudine is not recommended due to risk of overlapping myelosuppression.• Rituximab, a monoclonal anti-CD20 antibody.

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