Prof.K.H.NOORUL AMEEN’s UnitDr.E.Thirulogachandar

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

HOPI: Apparently normal 3 weeks before.

H/o headache-20 days bifrontal dull aching continuous not ass. with nausea/vomiting

No h/o feverNo 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

h/o nasal regurgitationh/o diff. in speakingh/o diff in getting from squatting posture h/o diff in lifting arm above shoulderh/o flail limbs+No h/o diurnal variationNo h/o radicular pain or other sensory

disturbances No h/o autonomic or bladder disturbances

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

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

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

Cranial nerve right left

Olfactory N N

Optic nerve-visual acuity field colour vision fundus

6/6EqualNormalPapillodema+

6/6EqualNormalPapillodema+

3,4 and 6 nerves- extraocular movementsLight reflexAccomodation reflex

weakEqualConvergence absent

Weak Nystagmus+EqualConvergence absent

5th nerve Normal normal

7th nerve normal LMN palsy

8th nerve normal normal

9&10th nerve weak weak

11th nerve weak weak

12th nerve - LMN palsy

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-normalAutonomic nervous system-normalSpine&cranium-normal

Other system: CVS-S1 S2 normally heard no murmur RS- NVBS no added sounds Abdomen-soft; no organomegaly

Problems : insiduous onset over 20 days

1.Headache2.Asymmetrical multiple cranial nerve palsies3.Proximal weakness of UL&LL of LMN type4.Neck stiffness5.Bilateral papillodema

Provisional diagnosis: BASAL MENINGITIS -?TB

Neurogist opinion?Demyelination-/NMJ disorder?Basal meningitis –Tb started on empirical ATT with steroids After imaging and CSF analysis reviewed advised to continue ATT

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

MRI BRAIN T1 weighted image and contrast: Diffuse pachymeningeal enhancement

bilaterally and subarachnoid space in optic nerve sheath appears prominent

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 seenNegative

Pt improved with ATT and steroidsCranial nerve palsies improved except 6th

nervePapillodema-resolving

But he developed clinically severe anamia and had mild splenomegaly over a period of 7 days later it became moderate ,no lymphadenopathy.

DD for diffuse dural enhancement1.Bacterial infections2.Non-infectious-Calavarial metastasis Extensive subdural

haematoma3.Low intracranial pressure states4.Hypertrophic cranial pachymengitis5.Wegner’s granulomatosis6.Multiple sclerosis7.Secondaries –breast/prostate carcinoma

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

PS study done outside:RBC-microcytic hypochromic

anisopoikilocytosis Many target cellsWBC-leukopenia+ ,no blast cellsPLT-reduced

USG abd-splenomegalyLFT-normalHIV-negativeSr.LDH-4011U/L

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

DIAGNOSIS Acute lymphocytic leukemia-L3 with leukemic meningitis CNS 3;

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

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 NeuroscienceVolume 17, Issue 10, October 2010, Pages 1252-1255

 

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

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 –

polyradiculopathyhydrocepalus

InvestigationsCSF 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%

12-year-old boy with acute lymphocyticleukemia presenting with severe headache

AML ALL

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

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)

Survival UNTREATED ALL pts with CNS features -- 4-6

WEEKS

ON TREATMENT – 9 – 24 WEEKS

> 1 YEAR SURVIVAL

RATE – 10 %

.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%)

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.

Clinical featuresFeature 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

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

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

Neurological manifestations of leukemia

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.

3.Less common symptoms include myelopathy, auditory symptoms vertigo, ataxia, and hallucinations.

4. Diffuse dural infiltration by leukemia, far less common than leptomeningeal involvement

Nonmeningeal DiseaseIntracranial 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 .

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

Factors Responsible for Cerebral Infarction

AtherosclerosisNonbacterial thrombotic endocarditisIntravascular coagulationSinovenous occlusionTumor emboliSeptic emboliMiscellaneous (e.g. , compression of artery

by tumor, vasculitis)L-asparaginase therapy (leading to

sinovenous thrombosis

Pecularities of this case

Presenting initially as basal meningitisAsymmetetrical cranial nerve palsies with

polyradiculopathyDural enhancement on MRI in CNS ALL

which is rare.Absence of blast cells in peripheral blood.

Carry home message

Pt presenting with cortex involvement,multiple cranial nerve palsies and polyradiculopathy DD are

1.Tb meningitis when associated with fever2.if no fever suspect carcinomatous

meningitis.

References :American journal of radiology-165

SEPTEMBER-1995Brain ‘s neurologyAdam ‘s neurologyWilliam’s haematology-8th editionMRI IMAGING -SUTTON

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