MEDICAL GRANDROUNDS

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MEDICAL GRANDROUNDS

• Marion Priscilla B. Aurellado, M.D.
• May 22, 2008

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Objectives

• To present a case of cerebral toxoplasmosis
• To discuss an approach to right upper extremity
  weakness in a young, previously healthy patient
  with mass lesions in the brain on imaging
• To present some epidemiologic data on the burden
  of HIV/AIDS in the Philippines

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Identifying Data

• J.E.
• 27 year old male
• Single
• Filipino
• Roman Catholic
• From Pangasinan

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Chief Complaint

• Near syncopal attack

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History of Present Illness

• 3 months

• Intermittent dizziness
• Light headedness
• No meds/consult

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History of Present Illness

• 2 weeks

• RUE weakness
• Weak hand grip
• Orthopedic consult done
• Unrecalled meds given
• Advised observation
• Progression of right weakness
• Follow-up consult done
• EMG-NCV advised, but not done

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History of Present Illness

• 2 days
• Admission

• generalized body weakness
• Near syncopal attack
• Clinic consult done
• Hypotensive at 80/60
• Advised admission

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Review of Systems

• () weight loss 30 lbs in 4 months
• () undocumented intermittent fever chills
  since 4 months
• () anorexia
• () hair loss
• (-) headache
• (-) loss of consciousness
• (-) cough or colds

• (-) chest pain
• (-) dyspnea
• (-) palpitations
• (-) abdominal pain
• (-) nausea or vomiting
• (-) LBM/constipation
• (-) melena
• (-) hematochezia
• (-) dysuria
• (-) hematuria

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Past Medical History

• No asthma
• No DM
• No history of hepatitis
• No previous hospitalizations
• No history of blood transfusions
• No known food or drug allergies

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Family History

• () DM

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Social History

• Non-smoker
• Occasional alcoholic beverage drinker
• No illicit drug use

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Physical Examination

• General Survey
• Conscious, coherent, not in respiratory distress
• Vital Signs
• BP lying 100/60 BP sitting 100/60
• BP standing 80/50 CR 88 RR 18 afebrile
• HEENT
• Pink palpebral conjunctivae, anicteric sclerae,
  (-) tonsillopharyngeal congestion, (-) cervical
  lymphadenopathies

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Physical Examination

• Chest Lungs
• Symmetric chest expansion, clear breath sounds
• CVS
• Adynamic precordium, normal rate, regular
  rhythm, no murmurs
• Abdomen
• Flat abdomen, normoactive bowel sounds, no
  tenderness, no organomegaly

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Physical Examination

• Extremities
• Full and equal pulses, no edema, () purplish
  skin rash all over, () atrophy of dorsal
  interossei muscles of right hand (claw hand
  appearance), () subcutaneous nodules in all
  extremities

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Neurologic Examination

• Mental Status Exam
• awake, oriented to 3 spheres
• no memory lapses, good attention
• intact repetition, recall 3/3
• no aphasia, no R-L disorientation

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Neurologic Examination

• Cranial Nerves
• CN I - intact CN II pupils 3-4 mm EBRTL,
  visual fields intact CN III, IV, VI primary
  gaze midline, full EOMs CN V intact V1-V3 CN
  VII no facial asymmetry CN VIII - intact CN
  IX, X intact gag CN XI good SCM tone CN XII
  tongue midline

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Neurologic Examination

• Sensory Intact to all modalities
• Motor 5/5 on both lower extremities and LUE
• RUE 5-/5 shoulder abduction 4/5 shoulder
  adduction 4/5 Shoulder extension 5-/5
  shoulder flexion 5-/5 elbow flexion 4/5 elbow
  extension

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Neurologic Examination

• Cerebellum No dysdiadochoinesia, no dysmetria,
  able to walk in tandem, walk on heels and toes
• Deep Tendon Reflexes 2 left 3 right upper
  extremity, 2 right lower extremity
• Pathologic Reflexes no Babinski
• Meninges no nuchal rigidity

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Salient Features

• 27 year old male
• Previously healthy
• Right upper extremity weakness, dizziness
• Significant weight loss anorexia
• Intermittent fever
• Generalized skin rash
• Atrophy of dorsal interossei muscles of right
  hand (claw hand appearance)
• Subcutaneous nodules in all extremities

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Where is the Lesion?

• Focal peripheral nerve involvement

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What is the Nature of the Lesion?

• Metabolic
• Inflammatory
• Trauma
• Thomas PK, Ochoa J. Symptomatology and
  differential diagnosis of peripheral neuropathy.
  In Dyck PJ, Thomas PK, eds. Peripheral
  neuropathy. Philadelphia Saunders, 1993749-74.

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Admitting Impression

• Connective Tissue Disease

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Course in the Wards

• 12 L ECG
• Stat 5
• IV Fluids started
• ESR and ANA
• EMG-NCV

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1st Hospital Day

• BP stable 100-110/60-70
• No dizziness
• () R arm weakness
• ESR 120
• Impression Connective tissue disease

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2nd Hospital Day

• Prednisone started
• EMG NCV R arm - NORMAL
• ANA negative
• Impression Connective tissue disease ruled out

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2nd Hospital Day

• Repeat CBC
• Anemia eosinophilia
• Fecalysis
• Dermatology referral Skin biopsy
• Impression Parasitic infection
• MRI MRA with Gadolinium

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Salient Features

• Subcutaneous nodules in all extremities
• Anemia, eosinophilia
• Multiple ring enhancing lesions on cranial MRI
• Impression T/C Neurocysticercosis
• R/O CNS Malignancy

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Multiple Ring Enhancing Lesions on MRI
Infectious
Neoplastic
Primary
Metastatic
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Multiple Ring Enhancing Lesions on MRI
Infectious
Neoplastic
Bacterial Abscess
Tuberculoma
Toxoplasmosis
Cryptococcus
Neurocysticercosis
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Primary CNS Lymphoma

• Present with one of 3 syndromes
• Subacute progression of focal neurologic deficit
• Seizure
• Nonfocal neurologic deficit Headache
• Fever, malaise, weight loss, anorexia suggest
  metastatic more than primary
• Uniformly enhancing mass lesion in
  immunocompetent
• Ring enhancing in the immunocompromised

?
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Metastatic Brain Tumors

• Most commonly originates from
• Lung CA
• Breast CA
• GI malignancy
• Melanoma

?
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Bacterial Brain Abscess

• Cause Streptococcus (40), Anaerobes,
  Staphylococcus (10)
• Associated with otitis, mastoiditis, dental
  infections or head trauma
• Headache is the most common symptom in gt75 of
  cases
• Classic triad of headache, fever, and focal
  neurologic deficit
• Multiple ? hematogenous ? poorly encapsulated

?
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Tuberculoma

• Uncommon manifestation of CNS tuberculosis
• Cause Mycobacterium tuberculosis
• Transmission Hematogenous spread from a primary
  pulmonary or postprimary pulmonary disease
• Seizures or focal neurologic deficits
• Diagnosis AFB on CSF

?
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Neurocysticercosis

• Cause Taenia solium
• Transmission Ingestion of undercooked pork
• Cysticerci found anywhere in the body but are
  commonly in
• Brain
• CSF
• Skeletal muscle
• Subcutaneous tissue
• Eye

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Neurocysticercosis

• Often presents with seizures and signs of
  increased intracranial pressure
• Diagnosis
• Fecalysis
• Neuroimaging
• Evidence of cysticercosis outside the CNS

?
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Cryptococcosis

• Cause Cryptococcus neoformans
• Transmission inhalation of yeast from the
  environment (bird droppings)
• Risk factor CD4 lt 100
• Presents with headache, fever, cranial nerve
  paresis, and meningeal irritation
• Diagnosis India ink stain, CALAS

?
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Toxoplasmosis

• Cause Toxoplasma gondii
• Transmission Ingestion of faecally contaminated
  material, Ingestion of undercooked meat
• Risk factor CD4 lt 100
• Asymptomatic in immunocompetent people

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Toxoplasmosis

• In immunocompromised, mainly involve the CNS
• Altered mental status (75)
• Focal neurologic deficits (60)
• Headaches (56)
• Seizures (33)
• Diagnosis
• Serology IgG and IgM

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3rd Hospital Day

• Mannitol started
• Lumbar puncture done
• Opening pressure 120 cmH2O
• Clear
• WBC 2 Lymphocytes 2 RBC 0
• Sugar 64 (nv 40-75) Protein 47.4 (15-45)
• No organisms or pus cells
• Negative for AFB, India Ink, KOH, CALAS
• Dexamethasone started

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4th Hospital Day

• X-ray of the left femur NORMAL
• Infectious Diseases referral
• History of unprotected sex with multiple sexual
  partners and bisexual contacts
• HIV screening
• Whole abdomen UTZ NORMAL

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Multiple Ring Enhancing Lesions on MRI
Infectious
Neoplastic
Primary
Metastatic
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Multiple Ring Enhancing Lesions on MRI
Infectious
Neoplastic
Bacterial Abscess
Tuberculoma
Toxoplasmosis
Cryptococcus
Neurocysticercosis
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8th Hospital Day

• CD4 count
• Serum CALAS
• Toxoplasma IgG
• Toxoplasma IgM

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9th Hospital Day

• Discharged, awaiting final report
• Serum CALAS
• Toxoplasma IgG
• Toxoplasma IgM
• CD4 titers and HIV test

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Patient Outcome

• HIV () CD4 53
• Toxoplasma IgG 3.8 (nv lt2)
• Toxoplasma IgM 0.34 (nv lt0.5)
• Serum CALAS NEGATIVE

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Clinical Correlation
Toxoplasmosis Patient JE
Nonfocal to focal neurologic deficits Motor deficit (RUE)
Meningeal involvement uncommon Absence of meningismus
CSF often unremarkable, may have modest increase in cell count protein but normal glucose Sugar 64 (nv 40-75) Protein 47.4 (15-45)
CD4 lt 100 CD4 53
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Clinical Correlation
Toxoplasmosis Patient JE
() IgG titers detected as early as 2-3 weeks after infection Toxoplasma IgG 3.8 (lt2) Toxoplasma IgM normal
Multiple discrete high signal foci, heterogenous w/ well-circumscribed margins, and hyperintense on post contrast MRI Multiple ring enhancing lesions with vasogenic edema in both cerebral hemispheres at the corticomedullary margin
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Final Diagnosis

• Cerebral Toxoplasmosis
• HIV infection
• Atopic Dermatitis

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Management

• Toxoplasmosis is rapidly fatal if untreated
• Treatment of choice
• Pyrimethamine plus folinic acid plus sulfadiazine
  
• Pyrimethamine plus folinic acid plus clindamycin
• Danneman et al. Ann Intern Med 1992 11633-43.
• 6 weeks therapy at least, or until 3 weeks after
  complete scan resolution
• Corticosteroids for raised intracranial pressure
• Cohn et al. Am J Med 1989 86 521-7

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Management

• Oral co-trimoxazole is effective in doses of 2
  tablets 4 times daily for 1 month followed by 2
  tablets twice daily as secondary prophylaxis for
  life
• Lifetime prophylactic therapy for toxoplasmosis
  would only apply if patients are not receiving
  antiretroviral therapy with the CD4 count being
  under 200 cells/µl
• P Francis, January 2004, Vol. 94, No. 1 S Afr Med
  J

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HIV Ab Seropositives by YearHIV/AIDS Registry,
January 1984-July 2007 (N2,916
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HIV Ab Seropositives by Gender and Age
GroupHIV/AIDS Registry, January 1984-July 2007
(N2,916)
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Reported Modes of TransmissionHIV/AIDS Registry,
January 1984-July 2007 (N2,916)
Mode Jan 84 -July 07 July 07
Heterosexual Contact 1781 10
Homosexual Contact 567 9
Bisexual Contact 200 9
Blood/Blood product 19 0
IV drug use 7 0
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Reported Modes of TransmissionHIV/AIDS Registry,
January 1984-July 2007 (N2,916)
Needle prick injuries 3 0
Perinatal 44 0
No exposure reported 295 3
TOTAL 2916 31
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Patient Outcome

• Readmitted after 2 weeks for seizure
• Started on Co-trimoxazole and ARTs
• Discharged against medical advice
• Went back to Pangasinan
• Lost to follow-up
• AMD notified by company physician that the
  patient expired

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Thank you!!!