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A Case of Leukaemic Meningitis

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  • 1. Prof.K.H.NOORUL AMEEN’s Unit Dr.E.Thirulogachandar
  • 2.
    • A 20 yr old male admitted with
    • c/o headache-20 days
    • Double vision 7 days
    • Diff in swallowing – 7 days
    • Nasal regugitation-7 days
    • Diff in getting up from bed-1 week
  • 3.
    • HOPI:
    • Apparently normal 3 weeks before.
    • H/o headache-20 days bifrontal dull aching continuous not ass. with nausea/vomiting
    • No h/o fever
    • No h/o seizures,syncope,trauma
    • h/o double vision 1 week ,binocular more on lateral gaze and down gaze
    • h/o diff in swallowing both solids and liquids
  • 4.
    • h/o nasal regurgitation
    • h/o diff. in speaking
    • h/o diff in getting from squatting posture
    • h/o diff in lifting arm above shoulder
    • h/o flail limbs+
    • No h/o diurnal variation
    • No h/o radicular pain or other sensory disturbances
    • No h/o autonomic or bladder disturbances
  • 5.
    • Past history: h/o jaundice 2 yrs before and taken native treatment
    • no h/o food poisoning,dysentry,recent vaccination
    • Personal history: nil significant
    • Family history:nil significant
  • 6.
    • O/E pt
    • conscious,
    • oriented,
    • afebrile,
    • anaemia+
    • no jaundice,cyanosis,clubbing,lymphadenopathy
    • no pedal odema
    • no neurocutaneous markers,no nerve thickening
    • neck stiffness+
    • Vitals:PR-82/min,BP-120/76mm Hg,RR-16/min
  • 7.
    • Higher mental functions:
    • conscious
    • oriented to time place and person
    • Rt.handed person
    • speech –lingual and gutteral dysarthria
    • attention-normal
    • calculation-normal
    • behaviour-normal
    • memory-normal
  • 8. Cranial nerve right left Olfactory N N Optic nerve-visual acuity field colour vision fundus 6/6 Equal Normal Papillodema+ 6/6 Equal Normal Papillodema+ 3,4 and 6 nerves- extraocular movements Light reflex Accomodation reflex weak Equal Convergence absent Weak Nystagmus+ Equal Convergence absent 5 th nerve Normal normal 7 th nerve normal LMN palsy 8 th nerve normal normal 9&10 th nerve weak weak 11 th nerve weak weak 12 th nerve - LMN palsy
  • 9.
    • Motor system
    • Bulk –equal
    • Tone-hypotonia in UL &LL
    • Power-proximal weakness in UL&LL (4-/5)
    • DTR-absent
    • plantar-flexor both sides
    • Sensory system –normal
    • Cerebellum-normal
    • Autonomic nervous system-normal
    • Spine&cranium-normal
  • 10.
    • Other system:
    • CVS-S1 S2 normally heard
    • no murmur
    • RS- NVBS
    • no added sounds
    • Abdomen-soft; no organomegaly
  • 11.
    • Problems :
    • insiduous onset over 20 days
    • 1.Headache
    • 2.Asymmetrical multiple cranial nerve palsies
    • 3.Proximal weakness of UL&LL of LMN type
    • 4.Neck stiffness
    • 5.Bilateral papillodema
  • 12.
    • Provisional diagnosis:
    • BASAL MENINGITIS -?TB
  • 13. Neurogist opinion
    • ?Demyelination-/NMJ disorder
    • ?Basal meningitis –Tb
    • started on empirical ATT with steroids
    • After imaging and CSF analysis reviewed
    • advised to continue ATT
  • 14. CBC-Hb-9gm% 31/8/10 X ray chest PA view-normal TC-4200 ECG-WNL DC-P53L43E2 URINE R/E-NORMAL ESR-15/32 Na-142 MCV-77fl K -4.1 MCH-28.8 MCHC-33.5 SERUM-UREA-42mg/dl CREATININE-0.9mg/dl SUGAR-90 mg/dl
  • 15.  
  • 16.  
  • 17.  
  • 18.  
  • 19.  
  • 20. MRI BRAIN
    • T1 weighted image and contrast:
    • Diffuse pachymeningeal enhancement bilaterally and subarachnoid space in optic nerve sheath appears prominent
  • 21. LP CSF ANALYSIS Sugar 51 mg/dl (2/3 ofblood sugar) Protein 225mg/dl (40-60mg/dl) Cell count Acellular C & S (for pyogenic) NO GROWTH Chloride 113mEq/L(Normal 95-114)) Gram’s Staining AFB staining No Organism seen Negative
  • 22.
    • Pt improved with ATT and steroids
    • Cranial nerve palsies improved except 6 th nerve
    • Papillodema-resolving
    • But he developed clinically severe anamia and had mild splenomegaly over a period of 7 days later it became moderate ,no lymphadenopathy.
  • 23. DD for diffuse dural enhancement
    • 1.Bacterial infections
    • 2.Non-infectious-Calavarial metastasis
    • Extensive subdural haematoma
    • 3.Low intracranial pressure states
    • 4.Hypertrophic cranial pachymengitis
    • 5.Wegner’s granulomatosis
    • 6.Multiple sclerosis
    • 7.Secondaries –breast/prostate carcinoma
  • 24. 6/9 RPT CBC-Hb-11.0GM 10/9/10 CBC-HB-4.1GM TC-4200 TC-3200 DC-P48L52 DC-P50L48E2 ESR-2/5 ESR-28/52 PLT-1.0 LAC PLT-<20000 MCV-90.6 MCH-30.6 MCHC-31.2 RBC-3.4 Million RBC-1.55 Million PS STUDY -THROMBOCYTOPENIA PS STUDY-THROMBOCYTOPENIA
  • 25.
    • PS study done outside:
    • RBC-microcytic hypochromic anisopoikilocytosis
    • Many target cells
    • WBC-leukopenia+ ,no blast cells
    • PLT-reduced
  • 26.
    • USG abd-splenomegaly
    • LFT-normal
    • HIV-negative
    • Sr.LDH-4011U/L
  • 27. HAEMATOLOGY-CBC-Hb-5.1 GM TC-7200 DC-P3L10Atypical cells87% PCV-15% ESR-45/95 PLATELETS-5000 PS STUDY-RBC-normocytic normochromic WBC-dec.neutrophils,atypical mononuclear cells PLT-REDUCED BMA –Dilute marrow,BLASTS-90%, Nuclear&cytoplasmic vacuolation ACUTE LEUKEMIA-ALL –L3
  • 28. DIAGNOSIS
    • Acute lymphocytic leukemia-L3
    • with leukemic meningitis CNS 3;
  • 29. Copyright ©2007 American Society of Hematology. Copyright restrictions may apply. Maslak, P. ASH Image Bank 2007;2007:6-00053 Figure 1. Blasts appear small with a thin rim of cytoplasm
  • 30. Acute leukemia presenting with blasts first found in the cerebrospinal fluid but not in the peripheral blood
    • we report nine patients with acute leukemia, symptoms suggestive of involvement of multiple cranial nerves, the spinal cord, and meningeal involvement. Moreover, we found that all these patients unexpectedly showed the presence of blasts in the cerebrospinal fluid (CSF) but not in the peripheral blood despite repeated examinations. Bone marrow examination confirmed the presence of acute leukemia in these patients. .
    • Journal of Clinical Neuroscience Volume 17, Issue 10 , October 2010, Pages 1252-1255
    •  
  • 31. Carcinomatous meningitis
    • Occurs in 5 % of all primaries ;
    • Most common –breast, lung ,prostate ,lymphoma and
    • leukemia ,melanoma ,git,
    • Mode of spread -1.hematogenous via choroid plexus
    • 2.parenchymal blood vessels –
    • virchow robin space
    • 3.microscopic vessel involvement
    • in arachnoid to subarachnoid space
  • 32. Clinical features
    • Symptoms
    • Signs
    • Headache ,nausea, vomiting –increased ICT ;
    • Backpain due to radiculopathy;
    • Focal or generalised seizures
    • No fever
    • Higher mental function
    • - mild memory loss-50%
    • -dementia -30%
    • Multiple cranial nerve palsies
    • with asymmetrical limb
    • weakness ( predilection for
    • third nerve-75 % )
    • seventh – 47 %
    • eighth -40 %
    • second -38 %
    • Papilledma -19 %
    • 60%-absent DTR –
    • polyradiculopathy
    • hydrocepalus
  • 33. Investigations
    • CSF analysis :
    • pressure >160 mm water
    • protein >0.5 g/l
    • glucose < 2.5 mmol /l (< 45 mg /dl)
    • lymphocytes > 5 cells / c.mm
    • CSF for malignant cells –
    • first sample positivity rate 54 %
    • repeat sample positivity 30 %
    • negative -10%
    • MRI BRAIN –T1 weighted images with gadolinium enhancement will show meningeal enhancement -30 to 70%
  • 34. 12-year-old boy with acute lymphocytic leukemia presenting with severe headache
  • 35. AML ALL
  • 36. LEUKEMIC MENINGITIS
    • 5 – 15 % of hematological malignancies
    • ALL -40 % AML – 7 % lymphomas -7 -30 %
    • Grading :
    • CNS 1 –no WBC
    • CNS 2 -<5 WBC /Blasts
    • CNS 3 > 5 wbcs/Blast cells or presence of multiple cranial palsies
  • 37.
    • Real time PCR analysis of CSF is an excellent
    • tool to assess occult CNS leukemia involvement
    • in patients with ALL and can possibly be used to
    • refine CNS status classification. (J Mol Diagn 2005,
    • 7:127–132)
  • 38. Survival
    • UNTREATED ALL pts with CNS features -- 4-6 WEEKS
    • ON TREATMENT – 9 – 24 WEEKS
    • > 1 YEAR SURVIVAL RATE – 10 %
  • 39. . J Clin Oncol 21:184-188. © 2003
    • CNS2 patients have a good prognosis (EFS 80%) that does not require any intensification of CNS-directed therapy. TLP patients have an inferior prognosis compared with the CNS1 group (73% v 80%)
  • 40. Treatment
    • Dutch Childhood Oncology Group showed that prophylactic cranial irradiation can be safely omitted from all children with ALL. 202a
    • CNS disease at the time of leukemia relapse in adults occurs in approximately 10 percent of cases.
    • intrathecal methotrexate, cytarabine, and hydrocortisone. Systemic high-dose methotrexate and cytarabine add to the CNS therapy.
  • 41. Clinical features Feature Children Adult Age (years)        <1 2 —    1–9 72–78 —    10–19 20–26 —    20–39 — 55    40–59 — 36   ≥ 60 — 9 Male 56–57 62 Symptoms        Fever 57 33–56    Fatigue 50 ?    Bleeding 43 33    Bone or joint pain 25 25
  • 42. Lymphadenopathy        None 30 51    Marked (>3 cm) 15 11 Hepatomegaly        None 34 65    Marked (below umbilicus) 17 ? Splenomegaly        None 41 56    Marked (below umbilicus) 17 ? Mediastinal mass 8–10 15 CNS leukemia 3 8 Testicular leukemia 1 0.3
  • 43. CNS status* paediatric adults    CNS1 67–79/60 92–95    CNS2 5–24/27 ?    CNS3 3/3 5–8    Traumatic lumbar puncture with blasts 6–7/10 ? Leukemic blasts in marrow (%)    <90 33/46 29    >90 67/54 71 Leukemic blasts in blood    Present 87/90 92    Absent 13/10 8
  • 44.
    • Neurological manifestations of leukemia
  • 45. Meningeal disease
    • 1.Infiltration of the meninges by leukemic cells may affect the dura, the leptomeninges, or both and may be diffuse or focal.
    • 2. presents as signs and symptoms of increased intracranial pressure, including headache, nausea and vomiting, irritability, lethargy, and papilledema [5]. Cranial nerve palsies may also be present.
  • 46.
    • 3.Less common symptoms include myelopathy, auditory symptoms vertigo, ataxia, and hallucinations.
    • 4. Diffuse dural infiltration by leukemia, far less common than leptomeningeal involvement
  • 47. Nonmeningeal Disease
    • Intracranial masses may occur in leukemia, although they are rare. Chloromas (granulocytic sarcoma, myeloblastoma) are masses composed of immature granulocytic cells. These lesions were first described by Burns in 1811 and named for their greenish colon on gross inspection.
    • Granulocytic sarcoma occurs primarily in patients with acute myelogenous leukemia .
  • 48.
    • in leukemic patients include hemorrhage (intraaaxial or extraaxial),more in acute promyelocytic leukemia
    • sinovenous thrombosis, (cns infiltration,leucostasis&L-Asparginase therapy)
    • cerebral infarctions.
    • CNS and other infections- Aspergillus,Mucor,Cryptococcus&Listeria
    Haematologic and cerebrovascular manifestations
  • 49. Factors Responsible for Cerebral Infarction
    • Atherosclerosis
    • Nonbacterial thrombotic endocarditis
    • Intravascular coagulation
    • Sinovenous occlusion
    • Tumor emboli
    • Septic emboli
    • Miscellaneous (e.g. , compression of artery by tumor, vasculitis)
    • L-asparaginase therapy (leading to sinovenous thrombosis
  • 50. Pecularities of this case
    • Presenting initially as basal meningitis
    • Asymmetetrical cranial nerve palsies with polyradiculopathy
    • Dural enhancement on MRI in CNS ALL which is rare.
    • Absence of blast cells in peripheral blood.
  • 51. Carry home message
    • Pt presenting with cortex involvement,multiple cranial nerve palsies and polyradiculopathy DD are
    • 1.Tb meningitis when associated with fever
    • 2.if no fever suspect carcinomatous meningitis.
  • 52. References :
    • American journal of radiology-165 SEPTEMBER-1995
    • Brain ‘s neurology
    • Adam ‘s neurology
    • William’s haematology-8 th edition
    • MRI IMAGING -SUTTON
  • 53.
    • THANK YOU

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